Gastric electrical stimulation with multi-site stimulation anti-desensitization feature

ABSTRACT

The disclosure is directed to gastric stimulation programmers, stimulators and methods for controlling delivery of gastric stimulation therapy to maintain the efficacy of the therapy over time. Maintaining the efficacy of gastric stimulation therapy may be possible by implementing one or more anti-desensitization features in a gastric stimulation controller or stimulator. As electrical stimulation therapy is continuously delivered to a patient, the stimulated tissue may become desensitized to the electrical stimulation therapy such that the beneficial effect of the electrical stimulation is diminished. Once desensitization occurs, the affected tissue may not respond favorably to electrical stimulation therapy. Application of one or more anti-desensitization features to control gastric stimulation therapy may reduce or prevent desensitization and effectively extend the efficacy of the therapy over time

This application claims the benefit of U.S. provisional application No.60/997,058, filed Oct. 1, 2007, the entire content of which isincorporated herein by reference.

TECHNICAL FIELD

The disclosure relates to implantable medical devices and, moreparticularly, implantable medical devices for gastric electricalstimulation.

BACKGROUND

Obesity is a serious health problem for many people. Patients who areoverweight often have problems with mobility, sleep, high bloodpressure, and high cholesterol. Some other serious risks also includediabetes, cardiac arrest, stroke, kidney failure, and mortality. Inaddition, an obese patient may experience psychological problemsassociated with health concerns, social anxiety, and generally poorquality of life.

Certain diseases or conditions can contribute to additional weight gainin the form of fat, or adipose tissue. However, healthy people may alsobecome overweight as a net result of excess energy consumption andinsufficient energy expenditure. Reversal of obesity is possible butdifficult. Once the patient expends more energy than is consumed, thebody will begin to use the energy stored in the adipose tissue. Thisprocess will slowly remove the excess fat from the patient and lead tobetter health. Some patients require intervention to help them overcometheir obesity. In these severe cases, nutritional supplements,prescription drugs, or intense diet and exercise programs may not beeffective.

Surgical intervention is a last resort treatment for some obese patientswho are considered morbidly obese. One common surgical technique is theRoux-en-Y gastric bypass surgery. In this technique, the surgeon staplesor sutures off a large section of the stomach to leave a small pouchthat holds food. Next, the surgeon severs the small intestine atapproximately mid length and attaches the distal section of the smallintestine to the pouch portion of the stomach. This procedure limits theamount of food the patient can ingest to a few ounces and limits theamount of time that ingested food may be absorbed through the shorterlength of the small intestine. While this surgical technique may be veryeffective, it poses significant risks of unwanted side effects,including malnutrition, and death.

Electrical stimulation therapy is an alternative to surgicalintervention and may be effective in treating obesity either alone or incombination with diet and exercise. For electrical stimulation therapy,a patient is fitted with an implanted electrical stimulator thatdelivers electrical stimulation pulses to the patient's stomach viaelectrodes carried by one or more leads. The electrical stimulationtherapy may be configured to induce a sensation of fullness or nausea inthe patient, thereby discouraging excessive food intake. In addition, insome cases, the electrical stimulation therapy may be configured toincrease or decrease gastric motility, reduce appetite or increasesatiety, or induce a sensation of abdominal discomfort on ingestion of ameal, so that caloric absorption is reduced. Hence, electricalstimulation therapy may be effective in causing weight loss bydiscouraging food intake and/or reducing caloric absorption.

SUMMARY

The disclosure is directed to various techniques for controllingdelivery of gastric electrical stimulation therapy to maintain theefficacy of the therapy over time. Maintaining the efficacy of gastricelectrical stimulation therapy may be possible by implementing one ormore anti-desensitization features in a gastric electrical stimulationprogrammer or gastric electrical stimulator. The anti-desensitizationfeatures may limit application of delivery of electrical stimulation toselected times, durations, frequencies, electrode combinations, and/ortissue sites. The anti-desensitization features may be implementedindependently or in combination with one another to reduce or delaydesensitization of gastric tissue, and thereby promote effective and/orprolonged therapy.

In one aspect, the disclosure provides a method comprising receiving arequest to deliver gastric electrical stimulation therapy to a patient,prohibiting delivery of the gastric electrical stimulation therapy ifthe request is received within a lockout period following a previousdelivery of the gastric electrical stimulation therapy, and permittingdelivery of the gastric electrical stimulation therapy if the request isnot received within a lockout period following the previous delivery ofgastric stimulation therapy.

In another aspect, the disclosure provides a system comprising astimulator that delivers gastric electrical stimulation therapy to apatient, and an external programmer that controls the stimulator todeliver the gastric electrical stimulation therapy, wherein one of theexternal programmer or the stimulator receives a request to deliver theelectrical gastric stimulation therapy to the patient, prohibitsdelivery of the gastric stimulation therapy by the stimulator if therequest is received within a lockout period following a previousdelivery of gastric stimulation therapy, and permits delivery of thegastric stimulation therapy by the stimulator if the request is notreceived within a lockout period following the previous delivery ofgastric stimulation therapy.

In an additional aspect, the disclosure provides an external programmerfor a gastric electrical stimulator, the programmer comprising a userinterface that receives a request to deliver the gastric electricalstimulation therapy to a patient, and a processor that controls thegastric electrical stimulator to prohibit delivery of the gastricelectrical stimulation therapy by the stimulator if the request isreceived within a lockout period following a previous delivery ofgastric electrical stimulation therapy, and permit delivery of thegastric electrical stimulation therapy by the stimulator if the requestis not received within a lockout period following the previous deliveryof gastric stimulation therapy.

In another aspect, the disclosure provides a gastric electricalstimulator comprising a stimulation generator that delivers gastricelectrical stimulation therapy, an interface that receives a request todeliver the electrical gastric stimulation therapy to a patient, and aprocessor that controls the stimulation generator such that thestimulator generator prohibits delivery of the gastric stimulationtherapy by the stimulator if the request is received within a lockoutperiod following a previous delivery of gastric stimulation therapy, andpermits delivery of the gastric stimulation therapy by the stimulator ifthe request is not received within a lockout period following theprevious delivery of gastric stimulation therapy.

In another aspect, the disclosure provides a method comprisingdelivering gastric electrical stimulation therapy from an implantablegastric electrical stimulator to a patient for a first period of time,and denying a patient request received by an external programmer todeliver the gastric electrical stimulation therapy from the implantablegastric electrical stimulator to the patient for a lockout period oftime following the first period of time.

In a further aspect, the disclosure provides a method comprisingdelivering electrical stimulation therapy to a gastrointestinal organ ofa patient for a first period of time, wherein the first period of timeis selected to produce a desired therapeutic effect for a second periodof time that extends at least in part beyond an end of the first periodof time.

In another aspect, the disclosure provides a gastric electricalstimulation device comprising an electrical stimulation generatorgenerates electrical stimulation therapy for a first period of time, andone or more implantable electrodes coupled to deliver the electricalstimulation therapy to a gastrointestinal organ of a patient, whereinthe first period of time is selected to produce a desired therapeuticeffect for a second period of time that extends at least in part beyondan end of the first period of time.

In another aspect, the disclosure provides an external programmer devicefor a gastric electrical stimulator, the programmer comprising aprocessor that controls the electrical stimulation generator to generateelectrical stimulation therapy for a first period of time for deliveryto a gastrointestinal organ of a patient, wherein the first period oftime is selected to produce a desired therapeutic effect for a secondperiod of time that extends at least in part beyond an end of the firstperiod of time.

In another aspect, the disclosure provides a method for gastricstimulation with reduced desensitization, the method comprisingdelivering first electrical stimulation therapy to a gastrointestinalorgan of a patient via a first electrode combination positioned at afirst position on the gastrointestinal organ for a first period of timegreater than or equal to approximately 30 seconds, and delivering secondelectrical stimulation therapy to the gastrointestinal organ via asecond electrode combination positioned at a second position on thegastrointestinal organ for a second period of time greater than or equalto approximately 30 seconds, wherein the first and second electricalstimulation therapies are configured to produce a substantiallyidentical therapeutic result.

In an additional aspect, the disclosure provides a gastrointestinalelectrical stimulation device comprising a first electrode combinationimplantable at a first position on a gastrointestinal organ of apatient, a second electrode combination implantable at a second positionon the gastrointestinal organ, and a stimulation generator that deliversfirst electrical stimulation therapy to the gastrointestinal organ viathe first electrode combination for a first period of time greater thanor equal to approximately 30 seconds, and delivers second electricalstimulation therapy to the gastrointestinal organ via a second electrodecombination for a second period of time greater than or equal toapproximately 30 seconds, wherein the first and second electricalstimulation therapies are configured to produce a substantiallyidentical therapeutic result.

The details of one or more embodiments of the disclosure are set forthin the accompanying drawings and the description below. Other features,objects, and advantages of the disclosure will be apparent from thedescription and drawings, and from the claims.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a schematic diagram illustrating an example implantablegastric electrical stimulation system.

FIG. 2 is a block diagram illustrating example components of animplantable gastric electrical stimulator that delivers gastricelectrical stimulation therapy.

FIG. 3 is a block diagram illustrating example components of a patientprogrammer that receives patient input and communicates with a gastricelectrical stimulator.

FIG. 4 is a conceptual diagram illustrating example electrode arrayspositioned on the stomach of the patent for delivery of gastricelectrical stimulation.

FIGS. 5A-5E are example timing diagrams illustrating different modes fordelivering electrical stimulation pulses.

FIG. 5F is a graph illustrating gastric distention during and followingapplication of stimulation within a therapy window.

FIGS. 6A, 6B and 6C are example timing diagrams illustrating continuouspulses and bursts of pulses delivered to the patient via two differentchannels.

FIGS. 7A, 7B, 7C, 7D, and 7E are example timing diagrams illustratingrelative timing of stimulation delivered via different channels.

FIGS. 8A, 8B and 8C are example timing diagrams illustrating bursts ofpulses having variations between bursts.

FIG. 9 is a flow diagram illustrating a method for delivering gastricstimulation therapy according to a lockout period that extends theefficacy of the therapy.

FIG. 10 is a flow diagram illustrating a method for delivering gastricelectrical stimulation therapy according to a combination of electrodesselected to extend the efficacy of the therapy.

FIG. 11 is a flow diagram illustrating a method for delivering gastricelectrical stimulation therapy at randomized start times to extend theefficacy of the therapy.

FIG. 12 is a flow diagram illustrating a method for selecting differentburst pattern characteristics for gastric electrical stimulation toextend efficacy of therapy.

FIG. 13 is a flow diagram illustrating application of a therapy windowfeature for gastric electrical stimulation to extend efficacy oftherapy.

FIG. 14 is a flow diagram illustrating application of a multi-sitestimulation feature for gastric electrical stimulation to extendefficacy of therapy.

DETAILED DESCRIPTION

The disclosure is directed to techniques for controlling delivery ofgastric stimulation therapy to maintain the efficacy of the therapy overtime. Maintaining the efficacy of gastric stimulation therapy may bepossible by implementing one or more anti-desensitization features in anexternal gastric stimulation programmer and/or gastric electricalstimulator to limit application of electrical stimulation to selectedfrequency, times, tissue sites, and/or durations. Theanti-desensitization features may be implemented independently or incombination with one another to reduce or delay desensitization ofgastric tissue, and thereby promote effective and/or prolonged therapy.

The gastric stimulator may be external or implantable. An externalstimulator may deliver stimulation via one or more percutaneouslyimplantable leads. An implantable stimulator may deliver stimulation viaone or more fully implantable leads. An external programmer such as apatient programmer or physician programmer may communicate with agastric electrical stimulator, e.g., by radio frequency (RF) wirelesstelemetry or other techniques. Gastric electrical stimulation generallyrefers to electrical stimulation of the stomach, small intestine orother organs within the gastrointestinal tract, and may alternatively bereferred to as gastrointestinal electrical stimulation.

Desensitization may generally refer to a state of accommodation in whichdelivery of electrical stimulation to a particular tissue site is lesseffective in achieving a desired therapeutic result. Incorporation ofanti-desensitization features in a programmer and/or stimulator mayallow gastric stimulation therapy to be more effective in treating thepatient for a longer period of time when compared to standard therapy.This extended period of effective therapy may reduce the chance that thepatient will need to pursue different treatment options due toelectrical stimulation desensitization. In addition, in some cases, oneor more anti-desensitization features may reduce the amount and durationof stimulation provided to the patient, which may conserve battery powerand extend the operational life of an implantable stimulator.

As electrical stimulation therapy is continuously delivered to apatient, the stimulated tissue may become desensitized to the electricalstimulation therapy such that the beneficial effect of the electricalstimulation is diminished. Once desensitization occurs, the affectedtissue may no longer respond favorably to electrical stimulationtherapy. Application of one or more anti-desensitization features tocontrol gastric stimulation therapy, either via an external gastricstimulation programmer or an implantable gastric stimulator, or both,may reduce or prevent desensitization and effectively extend theefficacy of the therapy over time.

In accordance with this disclosure, an external gastric stimulationprogrammer or gastric electrical stimulator may utilize one or moreanti-desensitization features that extend the efficacy of gastricstimulation therapy delivered to the patient by the gastric stimulator.The external gastric stimulation programmer may be, in some cases, apatient programmer that communicates within the gastric stimulator,e.g., by wireless telemetry. The anti-desensitization features mayinclude at least one of a lockout period feature, a therapy windowfeature, a multi-site stimulation feature, a therapy schedule feature, aburst pattern variation feature, and a burst pattern parameter selectionfeature.

After therapy has been delivered for a permitted period of time, eitherby way of a therapy window feature or otherwise, a lockout periodfeature may be applied by the programmer or stimulator to prevent thepatient from reinitiating further stimulation therapy until the lockoutperiod expires, thus preventing excessively frequent stimulation. If apatient attempts to reactivate stimulation before the lockout period hasexpired, the programmer or stimulator may prohibit delivery ofstimulation. In addition, the programmer may notify the patient thatstimulation cannot be activated until the lockout period has expired.

The length of the lockout period may be selected to ensure that subjecttissue has a sufficient period of time to recover between successiveapplications of electrical stimulation in order to avoid or delaydesensitization. The lockout period may be, for example, on the order ofseveral seconds, minutes or hours. The lockout period feature mayinterrupt stimulation for certain periods of time, which may allow timefor neurotransmitters to be replenished at the cell level.

Upon receipt of a request to delivery stimulation therapy, a programmeror stimulator may apply the lockout period feature to prohibit deliveryof the gastric electrical stimulation therapy if the request is receivedwithin a lockout period following a previous delivery of the gastricelectrical stimulation therapy, and deliver the gastric electricalstimulation therapy if the request is not received within a lockoutperiod following the previous delivery of gastric stimulation therapy.

Using a therapy window feature, the programmer or stimulator may permitdelivery of therapy for only a relatively short duration such that thepatient may rely upon residual stimulation effects to prolong a desiredtherapeutic effect after stimulation has been stopped. In this manner,the therapy window prevents stimulation for an excessive period of time.In some cases, the therapy window W may represent approximately aminimum duration of the gastric stimulation therapy that has beendetermined or estimated to be effective in producing desired therapeuticeffects for a desired period of time, including a period of time aftertermination of the gastric stimulation therapy. In some cases, thetherapy window W may represent approximately the minimum duration plus atime margin to ensure the desired therapeutic effect for the desiredperiod of time.

At the same time, although it may be determined as a function of theminimum duration sufficient to produce a therapeutic effect for adesired period of time, the therapy window W also may specify themaximum period for which stimulation may be delivered at a given time.If the minimum duration defining the therapy window W is sufficient toachieve a desired therapeutic effect for a given period of time, thendelivery of stimulation beyond this duration may be consideredinefficient. Accordingly, the therapy window W may specify the maximumduration of stimulation to be delivered, and at the same time bedetermined according to the minimum duration sufficient to achieve adesired therapeutic effect for a specified period of time.

If the minimum period of time sufficient to maintain a desiredtherapeutic effect for a desired period of time x, given a set ofstimulation parameters, is y minutes, then the therapy window W may beapproximately y minutes in length, possibly plus or minus a margin oftime. Hence, when the stimulator delivers stimulation during the therapywindow W, it may deliver stimulation for a maximum of y minutes.However, the therapeutic effect may be produced for x minutes.Application of stimulation for the length of the therapy window W, withappropriate stimulation parameters, may be sufficient to cause a desiredtherapeutic effect that remains at least partially intact for aprolonged period of time even after delivery of stimulation isterminated. In this case, a desired therapeutic effect can be achievedfor an extended period of time beyond the actual time that electricalstimulation is applied to the patient.

To implement the therapy window feature, a programmer or stimulator maydeliver electrical stimulation therapy to a gastrointestinal organ of apatient for a first period of time, wherein the first period of time isselected to produce a desired therapeutic effect for a second period oftime that extends at least in part beyond an end of the first period oftime. In this case, the first period of time corresponds to the therapywindow W, and the second period of time corresponds to the period oftime for which the desired therapeutic effect persists. The secondperiod of time, in some cases, may be greater than the first period oftime. The first period of time may be selected, in some cases, asapproximately a minimum period of time sufficient to produce the desiredtherapeutic effect for the second period of time. As an example, thedesired therapeutic effect may be a change in gastric muscle toneindicated by a degree of gastric distention. The degree of gastricdistention may correspond to a percentage increase in gastric volume.

The programmer or stimulator may apply a therapy schedule feature topermit delivery of stimulation therapy only during predetermined therapyschedule times S, e.g., coincident with ordinary meal or snack times forobesity therapy or motility regulation. The therapy schedule may becustomized for particular patients to match different meal times, snacktimes and lifestyles. Therapy windows W may be applied at differenttimes within a permitted schedule time S. Notably, the schedule time Sis different from the first and second periods referred to above withrespect to the therapy window feature, as well as the lockout perioddescribed above. In contrast, the schedule times specify times on aschedule at which stimulation may be delivered, possibly subject toother anti-desensitization features such as the lockout period andtherapy window features.

When delivery of stimulation therapy is requested at a time that doesnot fall within one of the predetermined therapy schedule time S on thetherapy schedule, the programmer or stimulator may prohibit delivery ofstimulation therapy. In addition, the programmer may notify the patientthat stimulation cannot be activated until the next permitted time S onthe therapy schedule. Hence, stimulation may be off between therapy timeS on the therapy schedule, helping to prevent or delay desensitizationof stimulated tissue. Delivery of stimulation therapy may be requestedby a patient or requested internally within a programmer or stimulatoras an automated request, e.g., according to a therapy schedule.

Using a multi-site stimulation feature, the programmer or stimulator mayselect different combinations of electrodes to deliver stimulation todifferent tissue sites at different times. The different times maypartially overlap or not overlap. The multi-site stimulation feature maybe applied such that different electrode combinations are used within atherapy window W, or within different therapy windows, or withindifferent periods of time on the therapy schedule, or when stimulationis otherwise applied. In this manner, the programmer or stimulator maydistribute electrical stimulation over a larger number of varied tissuesites over time to prevent rapid desensitization that could otherwiseoccur if stimulation was delivered to a single tissue site. In somecases, the selection of different electrode combinations for stimulationat different times may be ordered, randomized, or pseudo-randomized suchthat stimulation is delivered to different tissue sites over time inorder to prevent or delay desensitization of a particular tissue site.

As an example, to implement an multi-site stimulation feature, aprogrammer or stimulator may control delivery of gastric stimulation bydelivering first electrical stimulation therapy to a gastrointestinalorgan via a first electrode combination associated with a first positionon the gastrointestinal organ for a first period of time, and deliveringsecond electrical stimulation therapy to the gastrointestinal organ viaa second electrode combination associated with a second position on thegastrointestinal organ for a second period of time. The periods of timeused for the multi-site stimulation feature, like the periods used forthe lockout period and therapy window, are different from the therapyschedule periods P.

The electrode combinations used for the multi-site stimulation feature,may be associated with the positions on the gastrointestinal organ inthe sense that electrodes in the combinations are generally co-locatedwith the positions, or otherwise positioned to direct stimulation to thepositions as different stimulated tissue sites. In some cases, however,each electrode combination may include at least one electrode in commonwith one another, e.g., such as a common ground electrode on a devicehousing in a unipolar arrangement or elsewhere in a bipolar ormultipolar arrangement. In addition, at least some of the electrodesforming an electrode combination may be carried by the same lead ordifferent leads.

In some examples, each of the first and second periods of time may begreater than or equal to approximately 30 seconds. In this manner,stimulation may be applied to a tissue site for a period of timesufficient to support a desired therapeutic effect, but then be shiftedto another tissue site to mitigate tissue desensitization. In othercases, each of the first and second periods of time may be greater thanor equal to approximately one minute, five minutes, one hour, or oneday. The first and second periods may reside within different therapywindows W or different schedule periods P, or within the same therapywindows W or schedule periods P.

The first and second electrical stimulation therapies delivered todifferent tissue sites are configured to produce a substantiallyidentical therapeutic result, such as promotion of gastric distention,nausea or discomfort to discourage food intake by a patient. In otherwords, each electrode combination delivers stimulation with parametersselected to produce substantially the same result, such as gastricdistention. In some cases, the first and second electrical stimulationtherapies may be configured to reduce, increase, or maintain gastricmotility. In other cases, the first and second stimulation therapies areconfigured to not reduce, increase, or maintain gastric motility, andinstead to promote gastric distention, nausea or discomfort, asmentioned above.

Using the multi-site feature, the programmer or stimulator may controldelivery of stimulation via two or more different electrodecombinations, e.g., on an interleaved basis during a given therapywindow W or during different therapy windows. In this manner, thestimulation therapy is distributed among different tissue sites as it isdelivered to prevent rapid desensitization at a single tissue site. Forexample, stimulation may be delivered to a first electrode combinationassociated with a first tissue site and then delivered to a secondelectrode combination associated with a second tissue site, e.g., asinterleaved, alternating pulse trains, bursts, or the like, within agiven therapy window or therapy period. As mentioned above, thestimulation parameters, electrode combinations and associated tissuesites may be selected to support a substantially similar therapeuticeffect, yet reduce the amount of time each of the tissue sites receivesstimulation, thereby preventing of delaying desensitization.

The programmer or stimulator may apply a burst pattern variation featureas a further anti-desensitization feature to vary the timing and/orduration of burst patterns of stimulation delivered to a patient. Apulse burst generally refers to a group of stimulation pulses, e.g., bygating a continuous pulse train on and off. During the ON period, apulse burst is produced. A burst pattern, as used herein, generallyrefers to a set of multiple pulse bursts. To reduce or delaydesensitization, burst patterns can be produced by gating bursts ON andOFF. During the ON period, the stimulator delivers bursts of pulses.During the OFF period, no pulses or bursts are delivered. The pulsebursts can be gated ON and OFF repeatedly throughout the day to deliverburst patterns at selected times. The timing and/or duration of theburst patterns may be fixed during the day or varied. In either case,delivery of selected burst patterns instead of continuous bursts orcontinuous pulse trains may be effective in treating as well as inpreventing or delaying desensitization.

With the burst pattern parameter selection feature, the programmer orstimulator may vary one or more stimulation parameter values over aseries of burst patterns, as described above. For example, instead ofdelivering stimulation in continuous pulses, or bursts of pulses, theprogrammer or stimulator may control stimulation such that it isdelivered in burst patterns, wherein each burst pattern includesmultiple pulse bursts and each burst pattern is separated in time fromanother burst pattern. The programmer or stimulator may vary stimulationparameters such as amplitude, pulse width, and pulse rate of pulsesamong different burst patterns as another anti-desensitization feature,e.g., to prevent or delay desensitization of stimulated tissue.

The anti-desensitization features described above may be applied by aprogrammer, a stimulator or both to limit or prevent desensitization. Inaddition, the anti-desensitization features may be used individually orin combinations of two, three or more additional anti-desensitizationfeatures to extend or maintain efficacious therapy by preventing rapiddesensitization. In some cases, some or all of the anti-desensitizationfeatures may be applied by the programmer, stimulator, or both. Also, insome embodiments, one or more anti-desensitization features may beapplied by the programmer while one or more other anti-desensitizationfeatures may be applied by the stimulator. The anti-desensitizationfeatures may be applied by a programmer in selectively controlling astimulator via commands or requests transmitted to the stimulator, andmay be applied by a stimulator by controlling stimulation generated bythe stimulator.

In general, the disclosure is directed to methods for controllingdelivery of gastric electrical stimulation therapy to maintain theefficacy of the therapy over time. Gastric electrical stimulationtherapy may be delivered to the gastrointestinal tract, e.g., thestomach and/or small intestine, to treat a disease or disorder such asobesity or gastroparesis. In the case of obesity therapy, for example,electrical stimulation of the stomach may be configured to cause thestomach to undergo a change in gastric muscle tone, which may beindicated by distention, and induce a feeling of satiety within thepatient. As a result, the patient may reduce caloric intake because thepatient has a reduced urge to eat. Alternatively, or additionally,electrical stimulation of the stomach may be configured to induce nauseain the patient and thereby discourage eating. In addition, electricalstimulation of the duodenum may be configured to increase motility inthe small intestine, thereby reducing caloric absorption. Forgastroparesis, gastric stimulation of the stomach and/or duodenum may beconfigured to increase or regulate motility. In each case, however,consistent electrical stimulation of the same tissue over time maydesensitize the tissue to the electrical stimulation, resulting inaccommodation and reduced therapeutic efficacy.

Patients receiving implantable gastric stimulators may report an initialsensation that subsides over time. One explanation is that one or moreneurotransmitters necessary for depolarization of a nerve or muscle cellmay become depleted over time when a nerve or muscle cell is stimulatedcontinuously over time. There may be insufficient time for thisneurotransmitter to be replenished to a level sufficient for the nerveor muscle cell to fire in response to electrical stimulation. Thisresulting desensitization may cause diminished efficacy of theelectrical stimulation therapy to a point where the therapy is no longerbeneficial in treating the patient. For this reason, it may bebeneficial to implement one or more anti-desensitization features in thecontrol of the delivery of the therapy, either in a programmer orstimulator, to maintain the efficacy of the therapy.

One or more of the anti-desensitization features described in thisdisclosure may prevent or delay desensitization while also allowing thepatient to initiate the gastric stimulation therapy. A clinician may setthe anti-desensitization features when initially programming the gastricstimulation therapy or at any time throughout the duration of therapy.For example, a programmer may present a menu for the clinician to selectone or more desired anti-desensitization features to be applied to thestimulator individually or in various combinations. In some embodiments,the patient programmer may permit a patient to control the stimulator tostart delivery of gastric stimulation therapy, stop delivery of gastricstimulation therapy, and/or adjust one of more parameters associatedwith gastric stimulation therapy. In other cases, the patient may havelimited control or no control over the gastric stimulation therapy.

The patient programmer and stimulator may operate in a cooperative orcomplementary manner. The patient programmer may not permit the patientto control the stimulator in violation of the lockout period, therapywindow, and/or therapy schedule. Alternatively, the stimulator may denycommands received from the programmer that would violate the lockoutperiod, therapy window, and/or therapy schedule. Even if delivery ofstimulation is permitted, consistent with therapy windows, therapyschedules, and lockout periods, the programmer or stimulator mayimplement a burst pattern variation feature, a multi-site stimulationfeature, and/or a burst pattern parameter selection feature as describedin this disclosure.

For example, the stimulator may automatically apply the therapy windowfeature, multi-site stimulation feature, burst pattern variationfeature, and/or burst pattern parameter selection feature whendelivering stimulation therapy pursuant to a request from theprogrammer. Alternatively, when the programmer requests therapy, it mayfurther specify application of a therapy window feature, burst patternvariation feature, multi-site stimulation feature, and/or burst patternparameter selection feature by the stimulator. In some cases, theprogrammer may specify the particular electrodes, channels, andstimulation parameters to be applied by the stimulator in supporting thetherapy window feature, multi-site stimulation feature, and/or a burstpattern parameter selection feature.

The various techniques and features described in this disclosure may beimplemented within an external programmer, an external or implantablegastric electrical stimulator, or a combination of both. The externalprogrammer may be a patient programmer that accompanies a patientthrough a daily routine. Various examples of programmers, stimulatorsand associated functionality are provided for illustration, but withoutlimitation of the various aspects of the disclosure as broadly embodiedand described herein.

FIG. 1 is a schematic diagram illustrating an example implantablegastric stimulation system 10. System 10 is configured to preventdesensitization of a patient 16 to the gastric stimulation therapy.System 10 delivers gastric stimulation therapy to patient 16 in the formof electrical stimulation. Patient 16 may be a human or non-humanpatient. However, system 10 will generally be described in the contextof delivery of gastric stimulation therapy to a human patient, e.g., totreat obesity or gastroparesis. Gastric distention may generally referto an increase in gastric volume or a relaxation in gastric muscle tone.Hence, a volumetric change associated with gastric distention may beindicative of a state or relaxation of gastric muscle tone. In general,in accordance with this disclosure, gastric distention, increase ingastric volume and relaxation of gastric muscle tone may be usedinterchangeably to generally refer to a relative state of contraction orrelaxation of the stomach muscle.

The state of contraction or relaxation of the stomach muscle may beevaluated using a device called a balloon barostat. The Distender SeriesII™, manufactured by G&J Electronics, Inc., Toronto, Ontario, Canada, isan example of a balloon barostat system that may be used to diagnosecertain gastric motility disorders. Using this system, a balloon isinserted into the stomach, and inflated to a pressure just above theabdominal pressure, referred to the minimum distending pressure. Thebarostat is configured so that the pressure in the balloon is maintainedat a constant pressure. If the state of contraction of stomach muscledecreases, i.e., the state of relaxation of the stomach muscleincreases, then the balloon volume will increase. A decrease in thestate of stomach muscle contraction, if measured under conditions ofconstant balloon pressure, indicates a change in gastric muscle tone,i.e., gastric muscle relaxation, and is sometimes referred to as achange in gastric distention, gastric volume, or gastric tone. Moreparticularly, a decrease in muscle contraction corresponds to anincrease in muscle relaxation and promotes distention in terms anincrease in gastric volume using balloon barostat evaluation.

Gastric stimulation therapy is generally described herein as beingprovided to cause gastric distention, which may be associated with anincrease in gastric volume and indicate an increase in gastric muscletone relaxation. Alternatively or additionally, gastric stimulationtherapy may be delivered by system 10 to induce nausea, causeregurgitation, or cause other actions to treat certain patientdisorders. In other embodiments, gastric stimulation therapy parametersmay be selected to induce or regulate gastric motility, while in otherembodiments the gastric stimulation therapy parameters are selected notto induce or regulated gastric motility but to promote gastricdistention.

Inducing gastric distention in patient 16 causes the volume of stomach22 to increase, simulating a full or fuller stomach, and causing patient16 to feel prematurely satiated before or during consumption of a meal.Increased gastric distention and volume are generally consistent with adecreased state of stomach muscle contraction, which conversely may bereferred to as an increased state of stomach muscle relaxation. Whilegastric stimulation therapy is shown in this disclosure to be deliveredto stomach 22, the gastric stimulation therapy may be delivered to otherportions of patient 16, such as the duodenum or other portions of thesmall intestine.

As shown in FIG. 1, system 10 may include an implantable stimulator 12and an external patient programmer 14, both shown in conjunction with apatient 16. Implantable stimulator 12 may be referred to generally as anIMD. Patient programmer 14 and stimulator 12 may communicate with oneanother to exchange information such as commands and status informationvia radio frequency (RF) wireless telemetry. Stimulator 12 includes anelectrical stimulation generator that generates electrical stimulationpulses or continuous signals. For purpose of illustration, however, andwithout limitation, pulses will be generally described herein. In someembodiments, system 10 may further include a drug delivery device thatdelivers drugs or other agents to the patient for obesity or gastricmotility therapy, or for other nongastric related therapies. One or moreimplantable leads 18, 20 carry the electrical stimulation fromstimulator 12 to stomach 22. In other embodiments, stimulator 12 may beformed as an RF-coupled system in which an external controller providesboth control signals and inductively coupled power to stimulator 12within patient 16. Also, in alternative embodiments, system 10 may usean external, rather than implanted, stimulator, e.g., withpercutaneously implanted leads and electrodes.

Leads 18, 20 each may include one or more electrodes 24, 26 for deliveryof the electrical stimulation pulses to stomach 22. In the case ofmultiple electrodes attached to each lead 18, 20, the multipleelectrodes may be referred to as an electrode array. Combinations of twoor more electrodes on one or both of leads 18, 20 may form bipolar ormultipolar electrode pairs. For example, two electrodes on a single leadmay form a bipolar arrangement. Similarly, one electrode on a first leadand another electrode on a second lead may form a bipolar arrangement.Various multipolar arrangements also may be realized. A single electrode24, 26 on leads 18, 20 may form a unipolar arrangement with an electrodecarried on a housing of stimulator 12. Although the electricalstimulation, e.g., pulses or continuous waveforms, may be delivered toother areas within the gastrointestinal tract, such as the esophagus,duodenum, small intestine, or large intestine, delivery of stimulationpulses to stomach 22 will generally be described in this disclosure forpurposes of illustration. In the example of FIG. 1, electrodes 24, 26are placed in lesser curvature 23 of stomach 22. Alternatively, oradditionally, electrodes 24, 26 could be placed in the greater curvatureof stomach 22 or at some other location around stomach 22.

As mentioned above, gastric distention tends to induce a sensation offullness and thereby discourages excessive food intake by the patient.The therapeutic efficacy of gastric electrical stimulation in managingobesity depends on the stimulation parameters and stimulation target.Electrical stimulation may have mechanical, neuronal and/or hormonaleffects that result in a decreased appetite and increased satiety. Inturn, decreased appetite results in reduced food intake and weight loss.Gastric distention, in particular, causes a patient to experience asensation of satiety due to expansion of the stomach, biasing of stretchreceptors, and signaling fullness to the central nervous system.

While electrical stimulation to stomach 22 may cause gastric distension,tissue stimulated by the electrical pulses may not continue to react insubstantially the same manner after many pulses are delivered over aperiod of time. Electrical stimulation to the same tissue over anextended period of time such as hours, days or weeks may decrease theeffectiveness of the stimulation to the tissue. In particular, thetissue may become desensitized or accommodating of the stimulationtherapy. Therefore, the therapy becomes less effective to the point thatpatient 16 receives no further benefit from stimulating the same tissue.System 10 may include one or more anti-desensitization features,implemented by programmer 14, stimulator 12, or both. The features maybe designed to reduce the extent of desensitization, or prevent or delaydesensitization of stimulated tissue. The anti-desensitization featuresmay extend the efficacy of gastric stimulation therapy delivered to thepatient.

Reducing desensitization may involve limiting the amount of simulationdelivered to a specific tissue of stomach 22 over time. It may not benecessary to provide gastric stimulation therapy throughout the majorityof the day for patient. Instead, stimulation therapy may bepatient-initiated when patient 16 feels hungry and requires therapy toavoid ingesting excessive calories. In this manner, stimulation therapymay only be delivered to stomach 22 when needed.

One example anti-desensitization feature may be a lockout period thatprevents patient programmer 14 from directing stimulator 12 to delivergastric stimulation therapy upon receiving an indication from patient 16to start therapy. The lockout period may begin when stimulation therapybegins or when stimulation therapy is turned off. Generally, the lockoutperiod may be between approximately 5 and 240 minutes. Morespecifically, the lockout period may be between approximately 30 and 120minutes. The lockout period may vary in duration depending upon thefrequency of stimulation, the duration of stimulation, the time of day,patient condition, or other variables that may effect the desiredlockout period. For example, the lockout period may be 60 minutesbetween 7:00 AM and 12:00 PM, 90 minutes between 12:00 PM and 5:00 PM,and 120 minutes between 5:00 PM and 7:00 AM. The lockout periods mayalso change through the duration of therapy to prevent patient 16 fromadapting to the lockout period and circumventing therapy.

In operation, the patient may initiate delivery of electricalstimulation therapy by stimulator 12 via patient programmer 14 for apermitted period of time, which may be referred to as a therapy windowW, and which may constitute another type of anti-desensitizationfeature. The period of time could be, for example, one to two hours tocover an ordinary meal time. In addition, the period of time may beselected based on a therapy window desensitization feature, as describedelsewhere in this disclosure. Following a start of the delivery of thegastric electrical stimulation therapy, delivery of the gastricelectrical stimulation therapy may be terminated upon expiration of thetherapy window. After applying the stimulation therapy for the permittedperiod of time, patient programmer 14 would institute the lockout periodfeature such that the patient 16 is prohibited from restartingstimulation for a specified period of time (the lockout period)following termination of electrical stimulation therapy. As anillustration, if stimulation was active for a permitted period of timeof one hour, e.g., as specified by a therapy window or otherwise,following termination of the stimulation the patient 16 would not bepermitted to restart stimulation for the duration of a lockout period,e.g., 30 to 120 minutes, running from the end of the previousstimulation period.

Patient programmer 14 may be configured to start a clock or other timingdevice following termination of the electrical stimulation therapy inorder to time the lockout period. Once the lockout period has elapsed,patient programmer 14 may permit patient 16 to recommence delivery ofelectrical stimulation therapy. In particular, if the lockout period isexpired, an attempt by the patient 16 to initiate therapy via patientprogrammer 14 would be successful and the patient programmer would sendan appropriate command to stimulator 12 to start therapy. If the attemptis made during the lockout period, however, patient programmer 14 wouldnot send a command to stimulator 12 to start delivery of therapy.Instead, patient programmer 14 may generate a message to the patient 16indicating that the lockout period is in effect.

As an alternative, stimulator 12 may start a clock or timing device, andbe configured to refuse to accept or carry out an additional therapystart command from programmer 14 until a lockout period tracked by sucha timing device has expired. Hence, the lockout period feature may beimplemented in programmer 14, by refusing to transmit a stimulationstart command to stimulator 12 if the stimulation request is receivedwithin an active lockout period tracked by the programmer.Alternatively, stimulator 12 may implement the lockout period feature byrefusing to start stimulation in response to a stimulation start commandfrom programmer 14 if the command is received within an active lockoutperiod tracked by the stimulator. In this case, the stimulator 12 mayreceive the request from the patient via an external programmer viawireless telemetry. Stimulator 12 then may communicate the refusal toprogrammer 14, e.g., by wireless telemetry.

In either case, whether the lockout feature is enforced by stimulator 12or programmer 14, the programmer 14 may notify the patient 16 that thelockout period is active and that stimulation cannot be restarted. Thenotification may be communicated by audible, visual, and/or tactilemedia, such as a speaker, display or buzzer. In some embodiments,programmer 14 may notify the patient 16 of the lockout and advise thepatient of the time at which the lockout period will expire. In othercases, programmer 14 may indicate a running time or countdown of thelockout period, e.g., on a display or other user interface feature,which may discourage the patient 16 from even trying to startstimulation during the lockout period. Hence, a user interface of theprogrammer 14 may indicate at least one of a running time, a countdown,or an expiration time of the lockout period to a user.

With the lockout feature, a external programmer or an implantablegastric electrical stimulator may control delivery of gastric electricalstimulation therapy from an implantable gastric electrical stimulator toa patient for a first period of time, but deny a patient requestreceived by an external programmer to deliver the gastric electricalstimulation therapy from the implantable gastric electrical stimulatorto the patient for a second period of time following the first period oftime. In this case, the second period of time is the lockout period. Thepatient request may be received and processed by the patient programmerto impose the lockout period feature. Alternatively, the patient requestreceived by the external programmer may be transmitted to theimplantable gastric electrical stimulator, which then processes therequest to apply the lockout period feature.

Another example anti-desensitization feature is a therapy window thatdefines the duration of electrical stimulation. The therapy window maybe enforced by stimulator 12, programmer 14, or both. Once gastricstimulation is started, the therapy window may limit the duration of thestimulation to the length of the window in order to limit the amount ofstimulation delivered to the tissue. Generally, the therapy window maybe between approximately 1 and 60 minutes in duration. Morespecifically, the therapy window may be between approximately 3 and 30minutes in duration. Shorter or longer therapy windows may be necessaryto treat patient 16, depending upon stimulation parameters and patientcondition. Different therapy windows, i.e., of different lengths, may bepredetermined for different therapeutic effects and different periods oftime for which the therapeutic effects are desired. Accordingly, when adesired therapeutic effect is desired for a particular period of time,the effect and the time can be mapped to an appropriate therapy windowthat has been predetermined to support the effect and the time. Ingeneral, patient programmer 14 may initiate a clock or other timingdevice to track the running of the therapy window. When the therapywindow expires, patient programmer 14 may send a command to stimulator12 to stop delivery of stimulation therapy. Alternatively, such a clockor timer may be maintained within stimulator 12, such that a stopcommand from patient programmer 14 is not needed. Instead, stimulator 12may stop delivery when a clock or timing device within the stimulatorindicates that the therapy window has expired.

Patient physiology may support shorter therapy windows in order tofurther minimize desensitization of tissue in stomach 22. Afterdelivering electrical stimulation to stomach 22 that results in stomachdistention, stomach 22 may remain at least partially distended for aresidual recovery period of time during which the stomach transitionsfrom a distended state to a normal state. The at least partialdistention may be sufficient to retain a feeling of satiety, or othersensation discouraging food intake, in patient 16 during the recoveryperiod. In some cases, it may take stomach 22 between 30 and 60 minutesto recover from the stimulation induced distention and return to abaseline gastric volume level. In other words, the stomach may require30 to 60 minutes to decrease to a baseline volume from a 50% increased(distended) volume induced by stimulation. Consequently, system 10 maytake advantage of this “residual” distention of stomach 22 and deliverstimulation for a duration just long enough to effectively distend thestomach to a desired volume and subsequently turn off the stimulation,relying on the residual distention to effectively treat patient 16 for alonger period of time even though stimulation has been terminated. Inthis disclosure, the 50% increase is described for purposes ofillustration. However, other increase levels or other parameters may beselected as an indication of the desired therapeutic effect. Moreover,other types of desired therapeutic effects, in addition or as analternative to distention, may be use.

After stimulation is turned off, i.e., upon expiration of the therapywindow, the distention may remain above a desired level for a desiredperiod of time, e.g., at or above a 50% increase in gastric volume froma baseline gastric volume, e.g., as would be indicated by a balloonbarostat. For example, a desired therapeutic effect may be distentionthat causes an increase in gastric volume of at least 50% relative to apre-stimulation baseline value. In this case, 50% serves as a thresholdpercentage for the desired therapeutic effect. Hence, a delay inpost-stimulation recovery to the baseline volume may permit selection ofshorter therapy windows while still maintaining desired therapeuticresults beyond the expiration of the therapy windows.

In this manner, system 10 may further limit the duration of electricalstimulation and desensitization to the tissue adjacent electrodes 24,26. Again, a therapy window may be selected to promotestimulation-induced distention of the stomach to a desired volumeeffective in causing a feeling of satiety, with the knowledge thatresidual, post-stimulation distention may maintain the feeling ofsatiety for some time after termination of stimulation. The appropriatelength of the therapy window may be selected based on a determination orestimation of a length, i.e., a first period of time, sufficient toachieve a desired therapeutic effect for a desired period of time, i.e.,a second period of time.

The second period of time extends beyond the first period of time. Insome cases, the second period of time may be greater than the firstperiod of time. In other cases, the second period of time may be lessthan the first period of time. The second period of time, during whichthe desired therapeutic effect is maintained, may be inclusive of thefirst period of time, or overlap with at least a portion of the firstperiod of time, during which stimulation is delivered. The length of thefirst period of time defining the therapy window may be estimated basedon the length of a second period of time in which a typical therapeuticeffect is observed for a class of patients. Alternatively, the length ofthe first period of time may be determined for individual patients andcustomized based on therapeutic effect measured for such patients.

For an example therapeutic effect of gastric distention that causes anincrease in gastric volume from an initial volume, the first and secondperiods of time both may be on the order of a few minutes to a fewhours. For example, the first period of time during which stimulation isdelivered may be on the order of a few minutes to several minutes, whilethe second period of time, which is longer than the first period oftime, could be several minutes to a few hours. As one illustration, thefirst period of time could be approximately five minutes, while thesecond period of time, due to residual effects, may be approximately 30to 60 minutes. Alternatively, the first period of time could beapproximately one hour while the second period of time is approximatelyone and one-half hours, depending on the selected stimulation parametersand the physiological response of the patient.

Because battery longevity in an implantable stimulator is a paramountconcern, a shorter therapy window defined by the first period of timemay also provide a significant benefit in power reduction. Implantationof stimulator 12 in patient 16 requires surgery. Similarly, surgery maybe required for explanation of stimulator 12 in the event batteryresources are exhausted, as well as for re-implantation of a replacementstimulator. To reduce the number of surgical operations, and associatedpain, recovery time, and risks, it is desirable to preserve batteryresources to the extent possible while ensuring therapeutic efficacy.Because shorter electrical stimulation durations may reduce powerconsumption while increasing battery longevity, delivery of gastricstimulation therapy in addition to utilizing the residual distention ofstomach 22 to prolong therapeutic effects may achieve therapeuticefficacy in causing gastric distention while promoting batterylongevity. Even if a rechargeable battery is used, application of atherapy window feature may be effective in increasing the operating timebetween charges.

As discussed above, the therapy window may be selected, in someembodiments, as a first period of time during which stimulation must beapplied in order to produce therapeutic effects for a desired period oftime. This first period of time may be selected as approximately aminimum period of time sufficient to produce the desired therapeuticeffect for the second period of time. Accordingly, if the desiredtherapeutic effect is desired for the second period of time, then thefirst period of time is selected as approximately the minimum period oftime sufficient to support maintenance of the desired therapeutic effectfor the second period of time. The first period of time may vary basedon the patient and applicable stimulation therapy parameters, such ascurrent or voltage amplitude, pulse rate, pulse width, electrodeconfiguration and the like.

It may be determined or estimated for a particular patient or class ofpatients that electrical stimulation on the order of x minutes generallyproduces prolonged therapeutic effects on the order of z=x+y minutes,where y represents the number of minutes for which therapy is deemedeffective following termination of the application of stimulation energyduring the first period of time x. If the therapeutic effect does notreach a desired level until after stimulation has been delivered forpart of the first period of time, e.g., after m minutes, then the secondperiod of time may be equivalent to z-m minutes.

As an example, if the stimulation has parameters selected to causegastric distention, a physician or other caregiver may determine theparameters and duration of electrical stimulation sufficient to achievea desired volumetric change in the stomach, as well as the timefollowing termination of stimulation for which the volumetric changeremains in effect or remains above a threshold percentage, e.g., 50%above a baseline, pre-stimulation volume. The duration found to beeffective in producing the desired volumetric change and maintaining thevolumetric change or an acceptable percentage of the volumetric change,e.g., 50%, for a desired, second period of time may then be designatedas the therapy window used as the first period of time. The therapywindow may change according to the particular parameters applied forelectrical stimulation.

Patient programmer 14 or stimulator 12 may use the therapy window tolimit the time for which stimulation is applied, while ensuring that aprolonged therapeutic effect, such as gastric distention, is maintainedfor a desired period of time after cessation of stimulation. Hence, themaximum period of time specified by the therapy window as the firstperiod of time for delivery of stimulation may be selected as theminimum period of time sufficient to produce the desired therapeuticeffect for the second period of time, given the residual therapeuticeffect that remains following cessation of stimulation. As discussedabove, the therapy window may be estimated or determined empirically byclinical evaluation of a particular patient, e.g., by gastric volumeanalysis during and after application of stimulation for the particularpatient or a class of patient.

Hence, upon receiving a request to deliver gastric electricalstimulation therapy, a programmer 14 or stimulator 12 may deliver thegastric stimulation therapy for a first period of time as a therapywindow. Delivery of stimulation therapy may be requested by a patient orrequested internally within a programmer or stimulator as an automatedrequest, e.g., according to a therapy schedule. Again, the first periodof time may be selected as a function of an approximate duration of thegastric electrical stimulation therapy that is effective in producing adesired therapeutic effect for a second period of time. The secondperiod of time for which the desired therapeutic effect is produced maybe less than, equal to, or greater than the first period of time. Thefirst period of time that is sufficient to produce the desiredtherapeutic effect for the second period of time may vary according toselected stimulation parameters and stimulation site. The second periodof time may be the overall time for which a desired therapeutic resultis achieved.

The first period of time may be greater than or equal to a minimum timefor which stimulation is delivered in order to cause the desiredtherapeutic effect to last for the second period of time. In some cases,a small time margin may be added to this minimum time to produce thefirst period of time. Accordingly, the first period of time defining thetherapy window may be the minimum time or some other time that isselected or determined based on or as a function of the minimum time. Topromote anti-desensitization and conserve battery resources, however, itmay be desirable to select the first period of time to be approximatelya minimum period of time sufficient to produce the desired therapeuticeffect for the second period of time. Ordinarily, the first and secondperiods of time may overlap. The second period of time may subsist forsome time following expiration of the first period of time. In otherwords, the desired therapeutic effect for the second period of time maylast for some period of time after delivery of electrical stimulationtherapy has ceased. The first period of time limits the duration ofdelivery of stimulation to the patient. The second period of time is thetime for which a desired therapeutic effect produced by the stimulationremains in effect.

The desired therapeutic result may be a physiological response such as adegree of gastric distention, i.e., which may correlated with a degreeof gastric relaxation. A degree of gastric distention may be measured interms of an increase in a gastric volume that is at least 50% above abaseline or pre-stimulation level, i.e., a level of gastric volume priorto application of electrical stimulation. The 50% level is used forpurposes of illustration. Other target levels may also be specified,such as 35% or 65% above baseline levels. For example, before gastricelectrical stimulation is applied, a baseline gastric volume may bemeasured with a balloon barostat. Upon delivery of gastric stimulation,gastric volume begins to increase to a preselected gastric volume targetlevel of 50% above the baseline gastric volume level. Other targetlevels less than or greater than 50% may be specified, as mentionedabove, depending on the needs of the patient. Upon termination ofgastric stimulation, gastric volume may slowly decay from the targetlevel to the initial baseline level, pre-stimulation level, or someother level. The time during which gastric volume is at or greater thanthe target level may be considered to be the second period of timeduring which the desired therapeutic effect is maintained.

The amount of time that the gastric volume is above the target level isthe time during which the desired therapeutic effect is maintained, andmay be determined as follows. After insertion of a barostat balloon intothe stomach of a patient, and adjusting the balloon pressure to a levelabove the abdominal pressure at time t0, a baseline stomach volume maybe determined. Upon initiating gastric stimulation at time t1, gastricvolume begins to increase, reaching the example target level of 50%above baseline at time t2, and the maximum volume at time t3. The targetlevel of 50% above baseline volume may be referred to as the therapeuticthreshold.

After delivery of gastric electrical stimulation is discontinued at timet4, gastric volume may decline over time, decreasing to 50% abovebaseline by time t5, and returning to baseline levels by time t6. Thetherapy window T1 (=t4-t1) indicates the time during which electricalstimulation is delivered. The second period of time T2 (=t5-t2) that thegastric volume remains above the therapeutic level, i.e., producing thedesired therapeutic effect, generally extends beyond the stimulationtime T1, i.e., the first period of time or therapy window, during whichstimulation is applied. The overall second period of time T2 may begreater than or less than the stimulation time T1.

The actual times T1 and T2 may be measured in animals or humans usingdevices and techniques well known in the field of gastroenterology,including the balloon barostat. Other techniques or devices which assessthe state of tonic muscle contraction in the stomach may also be used todetermine the first and second periods of time T1 and T2 including thosethat measure changes in length or thickness of a segment of the stomachusing ultrasound, mechanical, optical, magnetic, or other electronictransducers.

As an illustration, the result may be a therapy window that permitsdelivery of stimulation within a therapy window of 5 minutes, with aprolonged effect of 30 minutes after cessation of stimulation. Hence,therapy may be delivered for only a first period of time T1 ofapproximately 5 minutes to achieve an overall desired therapeutic effectover a second period of time T2 of approximately 35 minutes (or somewhatless than 35 minutes in the event the desired therapeutic effect is notimmediately produced upon application of stimulation), which may beinclusive of the first period of time or a portion of the first periodof time. The second period of time may overlap with the first period oftime, but subsist for some period of time after cessation of delivery ofstimulation. In other words, the second period of time extends at leastin part beyond an end of the first period of time. In this manner,stimulator 12 only needs to deliver stimulation for a first period oftime T1 that is long enough to ensure a desired therapeutic effect overa desired second period of time T2.

By delivering stimulation for a first period of time selected to producea therapeutic effect for a second, desired period of time, rather thandelivering stimulation for the entire desired period of time for thetherapeutic effect, a stimulator may reduce power consumption and reducedesensitization that may result from prolonged delivery of stimulation.The ratio of the length of the therapy window to the length of time thatthe desired therapeutic effect remains substantially intact may varyaccording to the type of therapeutic effect, the patient, thestimulation parameters used to deliver the stimulation, electrodeconfiguration, stimulation target site, or other factors.

As another anti-desensitization feature, patient programmer 14,stimulator 12, or both may only permit stimulation to be deliveredaccording to a therapy schedule that specifies times during whichstimulation is permitted. Such times may be, for example, approximatelyone to three hour windows selected at or around ordinary meal times orsnack times. For example, patient programmer 14 may be configured topermit therapy delivery during time periods corresponding to ordinarybreakfast, lunch and dinner times, as well as snack times, if necessary.A therapy window specifying the maximum continuous time for whichstimulation may be delivered may be placed at different temporalpositions within such a time period.

In this manner, when a patient attempts to activate stimulation, patientprogrammer 14 may determine whether the activation request is madewithin one of the permitted time periods on the therapy schedule. If so,patient programmer 14 transmits a command to stimulator 12 to cause thestimulator to deliver therapy, possibly subject to other desensitizationfeatures, such as lockout period and therapy window features, e.g., asdescribed above. If the request is not made within a permitted timeperiod on the therapy schedule, patient programmer 14 does not send acommand to stimulator 12 to initiate therapy, and instead may generate anotification advising the patient 16 that therapy is not permitted atthe requested time.

As an alternative, stimulator 12 may be responsible for maintaining thetherapy schedule feature. In this case, programmer 14 may transmit acommand to start electrical stimulation therapy in response to a patientrequest. If stimulator 12 receives the command from programmer 14 withina permitted period of time on the therapy schedule, it may deliverstimulation. Delivery of stimulation may be subject to otheranti-desensitization features such as lockout period and therapy window.If stimulator 12 receives the command from programmer 14 at a time thatis not within a permitted period of time on the therapy schedule,stimulator refuses to deliver stimulation and may transmit a messagenotifying programmer 14 of such refusal, in which case the programmermay generate a notification for the patient 16.

The therapy schedule may be the same every day. To further prevent ordelay desensitization, however, the therapy schedule maintained byprogrammer 14 and/or stimulator 12 may be adjusted to vary the starttimes for the permitted periods of time, e.g., by minutes or hours.Hence, variation of the start time of the gastric stimulation throughouttherapy may provide another anti-desensitization feature. Whenstimulation is delivered to a specific tissue site at the same timeevery day, the tissue site may become desensitized to the stimulation asthe tissue becomes accustomed to the routine stimulation. In addition, apatient 16 may adjust his behavior due to routine stimulation byignoring the stimulation or changing behavior around the routinestimulation start times. Therefore, beginning stimulation at varyingstart times may help to reduce desensitization.

Different start times may be used every day, week, month, or at any timeduring therapy. The start times may vary by minutes or hours, asindicated above. Variation of the stimulation start times may beaccomplished by programmer 14 or stimulator 12 by cycling throughmultiple start times that have been pre-programmed by the clinician. Inother cases, stimulator 12 or programmer 14 may randomly select a starttime for each delivery of stimulation, possibly subject to someconstraints. For example, stimulator 12 or programmer 14 may select arandom start time within a preprogrammed range or the randomized starttimes may be weighted around a target start time.

In the case of weighted randomized start times, stimulator 12 may varystart times while still starting stimulation at some time near thetarget start time desired by the clinician and/or patient 16. Theweighting may be varied during therapy as well in order to further varystart times or accommodate a changing patient schedule. In general, itmay be desirable that the therapy schedule conform to meal and snacktimes. Therefore, permitted periods of time and associated start timeson the therapy schedule may vary but still be close to meal and snacktimes for the patient. As an illustration, a permitted period of therapyassociated with lunch may have a permitted start time that varies from11:30 one day, 12:00 the next day, and 11:45 the next day. As a furthermeasure, stimulator 12 or programmer 14 may be configured to vary endtimes of permitted periods of time during which stimulation may beapplied.

Alternatively, or additionally, multi-site stimulation may be providedas an anti-desensitization feature to vary the location of electricalstimulation to extend efficacious therapy of stomach 22. Multipleelectrodes may be located on stomach 22 and connected to stimulator 12.For example, electrodes 24, 26 may be electrode arrays in whichstimulator 12 may selectively activate one or more electrodes of thearrays during therapy to select different electrode combinations. Theelectrode combinations may be associated with different positions on thestomach or other gastrointestinal organ. For example, the electrodescombinations may be located at the different positions or otherwisepositioned to direct stimulation to the positions. In this manner,different electrode combinations may be selected to deliver stimulationto different tissue sites. The selection of electrodes forming anelectrode combination used for delivery of electrical therapy at onetime may change to a different selection of electrodes forming anelectrode combination for delivery of electrical therapy at a differenttime. The selection may vary between each delivery of stimulation or apredetermined number of delivery periods or total amount of deliverytime.

In general, to implement the multi-site feature foranti-desensitization, a programmer or stimulator may cause delivery offirst electrical stimulation therapy to a gastrointestinal organ of apatient via a first electrode combination associated with a firstposition on the gastrointestinal organ for a first period of time, anddelivery of second electrical stimulation therapy to thegastrointestinal organ via a second electrode combination associatedwith a second position on the gastrointestinal organ for a second periodof time. The first and second electrical stimulation therapies areconfigured to produce a substantially identical therapeutic result. Thedifferent electrode combinations may provide different stimulationchannels. As an example, stimulation delivered via the first and secondchannels may be configured to produce gastric distention, nausea ordiscomfort to discourage food intake by the patient. In some cases, thestimulation may be configured to regulate gastric motility. In othercases, the stimulation may be configured to not regulate motility, andinstead promote distention, nausea or discomfort.

A first electrode combination may include electrodes implanted at onelocation on the stomach, or elsewhere in the gastrointestinal tract, andthe second electrode combination may include electrodes implanted at adifferent location. In this manner, the stimulation therapy is deliveredto two or more different tissue sites. The first and second electrodecombinations may be implanted in the same gastrointestinal organ. Forexample, the first and second electrode combinations may both beimplanted in the stomach, or may both be implanted in the intestine.Each electrode combination may comprise two or more electrodes, whichmay be provided on one or more implantable leads. In some cases, anelectrode combination may include the device housing or can as anelectrode.

Each of first and second periods of time may be greater than or equal toapproximately 30 seconds, greater than or equal to one minute, greaterthan or equal to five minutes, greater than or equal to ten minutes,greater than or equal to one hour, or greater than or equal to one day.The first and second periods of time may partially overlap or notoverlap with one another. The first and second periods of time for whichstimulation is delivered to first and second electrode combinations,respectively, may be equal to or different from one another. In general,the first and second periods of time will not be coextensive.

By delivering stimulation to different electrode combinations atdifferent tissue sites at different times, desensitization of one tissuesite may be reduced. As the first and second periods of time arelengthened, however, a single tissue site may be exposed to stimulationfor an extended period of time. Accordingly, shorter periods of time onthe order of seconds, minutes, hours or days may be desirable, e.g., incontrast to weeks or months. Over the potentially lengthy operationallife of a stimulator, however, delivering stimulation via one electrodecombination for weeks or months followed by switching delivery to asecond electrode combination for weeks or months may still be desirable.

When the selection of electrode combination is changed, e.g., from thefirst period of time to a second period of time, patient programmer 14or stimulator 12 may determine the next selection of electrodes basedupon instructions defined by a clinician. The instructions may directthe selection to progressively move to the next set of electrodes in anelectrode array, move to the next electrodes that retain the desireddistance or orientation between electrodes, or randomly select the nextelectrodes to use for delivery of therapy. In the case of randomizedselection of electrodes, a new selection may be different than theprevious selection to avoid continued electrical stimulation exposure tothe same tissues. Stimulator 12 and/or patient programmer 14 may storeeach selection of electrodes used during the course of gastricstimulation therapy so that a clinician may review the selections andidentify any potential problems with the changing electrodes orineffective therapy with one or more electrodes being used.

In some cases, a multi-site stimulation feature may make use of three ormore electrode combinations. For example, a programmer or stimulator mayfurther cause delivery of third electrical stimulation therapy to thegastrointestinal organ via a third electrode combination associated witha third position on the gastrointestinal organ at a third time, repeatthe delivery of the first, second and third electrical stimulationtherapies for the first, second and third periods of time, and select anorder of the first, second and third periods of time in a varying orderfor at least some of the repeated deliveries. For example, in somecases, stimulation via the first, second, and third electrodecombinations may proceed in that order. Alternatively, stimulation couldproceed from first, to third, to second electrode combination, fromthird, to second, to first electrode combination, from third, to first,to second electrode combination, or in other orders. The first, secondand third electrical stimulation therapies may be configured to producea substantially identical therapeutic result. In some cases, the first,second and third positions are arranged such that the first position ismost proximal on the gastrointestinal organ, the third position is mostdistal on the gastrointestinal organ, and the second position is betweenthe first and third positions, where proximal refers to portions closerto the start of the gastrointestinal tract and distal refers to portionscloser to the end of the gastrointestinal tract.

For example, first and second electrode sets used to form first andsecond electrode combinations, respectively, may be displaced from oneanother by at least approximately 1 cm, more preferably at leastapproximately 3 cm, and still more preferably at least approximately 5cm. In some cases, the electrode combinations may be associated withpositions that are greater than 10 cm apart. As an illustration, thedifferent electrode sets could each be implanted within the lessercurvature of the stomach, but displaced approximately 5 cm from oneanother. In this manner, the different electrode combinations arepositioned to deliver stimulation to different tissue sites, and therebydelay or reduce likelihood of desensitization of a given tissuestimulation site. In general, first and second electrode sets may beimplanted a sufficient distance away from one another such that theytend to activate different tissue sites, or otherwise be implanted todeliver stimulation to tissue sites that are positioned a sufficientdistance away from one another. The first and second electrodecombinations may be placed at different positions on the same organ,such as different positions on the stomach or different positions on thesmall intestine. Alternatively, or additionally, the first and secondelectrode combinations may be placed at different positions on differentorgans, e.g., at one position on the stomach and another position on thesmall intestine.

Stimulator 12 and/or programmer 14 may control the stimulator to deliverstimulation via two or more different electrode combinations on atime-interleaved or time-independent basis. For example, stimulation maybe delivered via different electrode combinations on a time-interleavedbasis in different time slots, e.g., within a given therapy window orperiod of time on the therapy schedule. In this case, two or morestimulation channels may be active and controlled to deliver stimulationin respective time slots, which may partially overlap or not overlap. Inthis case, stimulation at different electrode combinations may bedelivered together within a therapy window, but on a time-interleavedbasis. Alternatively, stimulation may be delivered via differentelectrode combinations in separate therapy windows, such that eachelectrode combination is used separately and independently of oneanother. In this case, only one channel may be active at a time and maynot coordinate timing with another channel within a given therapywindow.

As described above, stimulator 12 may include a first channel coupled toa first set of electrodes forming a first electrode combination and asecond channel coupled to a second set of electrodes forming a secondelectrode combination. Additional channels, such as a third channelcoupled to a third set of electrodes, may be provided in someembodiments. Individual electrodes in the sets of electrodes may beselected to form electrode combinations, either among the electrodes oramong one or more electrodes and an electrode surface on a housing ofthe stimulator. Stimulator 12 may be configured to deliver stimulationwith identical, similar or different parameters via the first and secondchannels to achieve a substantially identical therapeutic effect.

As another anti-desensitization feature, programmer 14 and/or stimulatormay apply a burst pattern parameter selection feature to vary thecharacteristics of stimulation delivered to patient 16. For example, theburst pattern parameter selection feature may include varyingstimulation parameters of pulses within bursts of pulses delivered topatient 16. In one example, the stimulation parameters may be variedbetween at least two pulses within a single burst of pulses. Therefore,not all the pulses within a given burst have the same stimulationparameters. In another case, the stimulation parameters may be variedbetween the pulses of successive bursts of pulses. This variation ofstimulation parameters allows for each burst to have identical pulseswhile the pulses of subsequent bursts may be different. Additionally,the parameter selection feature may specify that a combination of pulsesare varied within a burst and between subsequent bursts.

As a further alternative, pulses may be delivered in burst patterns,where each pattern contains multiple pulse bursts. In this case, pulseparameters may be varied among different burst patterns. For example,first pulses in bursts associated with a first burst pattern may haveidentical pulse parameters, while second pulses in bursts associatedwith a second burst pattern may have one or more pulse parameters thatare different from pulse parameters associated with the first pulses inthe first burst pattern. Hence, successive burst patterns may have oneor more different pulse parameters. Alternatively, pulses within burstsin a first burst pattern may be varied relative to one another, andrelative to pulses within bursts in a second burst pattern. In addition,timing of bursts in different burst patterns may be varied.

The variation of stimulation parameters between pulses may be of slightmagnitude so that the stimulation pulses are not constantly the samewithout drastically changing the efficacy of the stimulation therapy asa whole. In other words, the variation in stimulation parameters may beonly directed to have an effect upon the desensitization of the tissueand not the overall effect of the perceived therapy. For example, astimulation parameter change from a previous pulse to a subsequent pulsemay differ by less than approximately ten percent, or less thanapproximately five percent. However, the stimulation parameters maychange by more than approximately ten percent in some cases wherestimulation efficacy is not affected by the larger magnitude changes.

The stimulation parameters that may be varied for the desensitizationmeasure may be current amplitude, voltage amplitude, pulse width, pulserate, and/or duty cycle. One or more stimulation parameters may bevaried at any given time, as long as the stimulation therapy remainseffective in treating patient 16. The progression of variation of thestimulation parameter changed to prevent tissue desensitization may beselected by the clinician during therapy programming. The stimulationparameter may cycle between preset parameter values specified by theclinician, vary randomly between a minimum limit and a maximum limit,vary with a weighted randomization that is centered to a target orprogrammed parameter value, or vary in some other way specified by theclinician. In any case, stimulator 12 may implement ananti-desensitization feature that varies the stimulation parameters overthe course of therapy in order to extend the efficacy of gastricstimulation therapy.

System 10 may implement more than one anti-desensitization feature atany given time. For example, system 10 may implement the lockout periodafter the therapy window has elapsed. In addition, the lockout periodand therapy window may be subject to the therapy schedule, and viceversa. In another example, system 10 may implement the lockout period inaddition to ordered, randomized, or pseudo-randomized selection ofelectrodes to vary the location of electrical stimulation periodicallythroughout therapy. In any case, the anti-desensitization feature usedby system 10 may be effective in extending therapy efficacy by reducingor preventing tissue desensitization that shortens the useful life ofelectrical stimulation therapy. The term “pseudo-random” may generallyrefer to a quasi random or effectively random output generated by asystem, such as software running on a microprocessor (e.g., randomnumber generators), and may be limited to a predetermined range ofvalues.

Stimulator 12 delivers electrical stimulation according to stimulationparameters stored within stimulator 12. In one example, stimulator 12delivers stimulation pulses with a pulse width selected to promotegastric distention and/or modulate gastric motility. A pulse width in arange of approximately 1 milliseconds to approximately 50 milliseconds,more preferably in a range of approximately 1.5 milliseconds toapproximately 10 milliseconds, more preferably approximately 2milliseconds to approximately 10 milliseconds, and even more preferablyapproximately 2 to 5 milliseconds, may be effective in causing gastricdistention while promoting better power conservation. As an example, thestimulation pulses delivered by stimulator 12 may have a pulse widthgreater than or equal to approximately 1 millisecond (ms), but generallyless than approximately 10 ms. More specifically, the pulse width may bebetween approximately 2 ms and 5 ms. Pulse widths in this range may belong enough to promote gastric distension but short enough that patient16 does not generally perceive significant negative effects from thestimulation, e.g., nausea, or cause excessive power consumption.

In another example, stimulator 12 may be programmed to produce feelingsof nausea to limit the desire of patient 16 to eat. In this case, pulsewidths may be generally greater than approximately 0.5 ms and as long asapproximately 50 ms. In still another example, stimulator 12 may deliverpulses with a pulse width greater than approximately 2 ms to reducemotility. In this case, the pulse width may be between approximately 1ms and approximately 100 ms. Other pulse widths may be used foradditional therapy outcomes. The clinician may program the stimulationparameters, such as the pulse width, amplitude, pulse rate, electrodecombinations and polarities, upon implant of stimulator 12 and possiblyin subsequent clinic visits, in order to appropriately treat thecondition of patient 16.

With further reference to FIG. 1, at the outer surface of stomach 22,e.g., along the lesser curvature 23, leads 18, 20 penetrate into tissuesuch that electrodes 24 and 26 are positioned to deliver stimulation tostomach 22. As mentioned above, the parameters of the stimulation pulsesgenerated by stimulator 12 may be selected to distend stomach 22 andthereby induce a sensation of fullness, i.e., satiety. In someembodiments, the parameters of the stimulation pulses also may beselected to induce a sensation of nausea. In each case, the inducedsensation of satiety and/or nausea may reduce a patient's desire toconsume large portions of food. Alternatively, the parameters may beselected to regulate motility, e.g., for gastroparesis. Again, thestimulation pulses may be delivered elsewhere within thegastrointestinal tract, either as an alternative to stimulation oflesser curvature 23 of stomach 22, or in conjunction with stimulation ofthe lesser curvature of the stomach. As one example, stimulation pulsescould be delivered to the greater curvature of stomach 22 locatedopposite lesser curvature 23.

For obesity therapy, the pulse width and/or other parameters may beselected so that electrical stimulation, when applied, causes at leastapproximately a twenty-five percent increase in gastric volume relativeto a baseline gastric volume, preferably at least approximately athirty-five percent increase in gastric volume, more preferably at leastapproximately fifty percent increase in gastric volume, more preferablyat least approximately a sixty-five percent increase in gastric volume,more preferably at least approximately a seventy-five percent increasein gastric volume, and still more preferably at least approximately aone-hundred percent increase in gastric volume. The increase in gastricvolume may be measured relative to a baseline gastric volume, such as apreprandial (pre-meal) and/or pre-stimulation gastric volume, and may bemeasured within a selected area of the gastrointestinal tract. Forexample, the gastric volume may be measured within the stomach ifelectrical stimulation is applied to the stomach. Alternatively, thebaseline and stimulation-induced gastric volume may be measuredelsewhere within the gastrointestinal tract if electrical stimulation isapplied elsewhere.

In addition to pulse width, the stimulation pulses are defined by otherparameters including current or voltage amplitude, pulse rate, and dutycycle. In some embodiments, stimulation parameters may further includeelectrode combinations and polarities in the event leads 18, 20 providemultiple electrode positions. As an illustration, in addition to a pulsewidth in the ranges identified above, stimulator 12 may generatestimulation pulses having a current amplitude in a range ofapproximately 1 to 20 milliamps (mA), preferably approximately 2 to 10mA, and more preferably approximately 3 to 6 mA. An example voltage maybe between approximately 0.5 volts and 10 volts. The pulse rate of thestimulation pulses may be in a range of approximately 0.05 to 50 Hertz(Hz), preferably approximately 1 to 50 Hz, more preferably approximately10 to 50 Hz, and more preferably approximately 20 to 50 Hz. As anillustration, a substantial amount of distention may be produced with apulse width of approximately 2 ms in combination with a pulse rate ofapproximately 40 Hz.

In addition, in some embodiments, stimulator 12 may deliver stimulationpulses with a duty cycle of approximately 50% ON/50% OFF, preferably 30%ON/70% OFF, and more preferably 20% ON/80% OFF. The pulses may begenerated in bursts, and the bursts may be generated in burst patternscontaining multiple bursts. Duty cycle generally refers to thepercentage of time that stimulator 12 is delivering stimulation pulsesversus the percentage of time during which the stimulator is idle, i.e.,not delivering pulses. During ON time, stimulator 12 delivers pulsesaccording to a set of parameters such as amplitude, pulse rate and pulsewidth. During OFF time, stimulator 12 does not deliver stimulationpulses to patient 16.

In addition, the duty cycle may include the amount of time stimulationpulses are delivered and the amount of time pulses are not delivered topatient 16 when the stimulator 12 is ON. Additionally, a higher levelduty cycle includes the amount of time stimulator 12 is ON and OFF. Inthis manner, example stimulation therapy may have duty cycles thatdescribe when stimulator 12 is ON and OFF in addition to cycles thatdescribe the amount of time pulses are delivered to patient 16 duringthe ON period. Stimulator 12 may also have nested duty cycles, such ascan be defined as bursts of pulses during an ON period of stimulation.Bursts of pulses and burst patterns will be further discussed below.

As one illustration, to cause gastric distention, stimulator 12 maydeliver stimulation pulses with an amplitude of approximately 1 to 10mA, a pulse width of approximately 2 to 10 milliseconds (ms), a pulserate of approximately 1 to 60 Hz, and a duty cycle of approximately 25%ON/75% OFF. As another illustration, stimulator 12 may deliverstimulation pulses with an amplitude of approximately 3 to 6 mA, a pulsewidth of approximately 2 to 5 milliseconds (ms), a pulse rate ofapproximately 20 to 50 Hz, and a duty cycle of approximately 40% ON/60%OFF. Such pulses may be delivered as bursts or burst patterns containingmultiple bursts. In each case, stimulator 12 may cause substantialgastric distention and a sensation of fullness, which may result inreduced food intake and, ultimately, weight loss.

Implantable stimulator 12 may be constructed with a biocompatiblehousing, such as titanium, stainless steel, or a polymeric material, andis surgically implanted within patient 16. The implantation site may bea subcutaneous location in the side of the lower abdomen or the side ofthe lower back. Stimulator 12 is housed within the biocompatiblehousing, and includes components suitable for generation of electricalstimulation pulses. Stimulator 12 may be responsive to patientprogrammer 14, which generates control signals to adjust stimulationparameters. As a further embodiment, stimulator 12 may be formed as anRF-coupled system in which an external controller such as patientprogrammer 14 or another device provides both control signals andinductively coupled power to an implanted pulse generator.

Electrical leads 18 and 20 are flexible and include one or more internalconductors that are electrically insulated from body tissues andterminated with respective electrodes 24 and 26 at the distal ends ofthe respective leads. The leads may be surgically or percutaneouslytunneled to stimulation sites on stomach 22. The proximal ends of leads18 and 20 are electrically coupled to the pulse generator of stimulator12 via internal conductors to conduct the stimulation pulses to stomach22 via electrodes 24, 26.

Leads 18, 20 may be placed into the muscle layer or layers of stomach 22via an open surgical procedure, or by laparoscopic surgery. Leads alsomay be placed in the mucosa or submucosa by endoscopic techniques or byan open surgical procedure. Electrodes 24, 26 may form a bipolar pair ofelectrodes. Alternatively, stimulator 12 may carry a reference electrodeto form an “active can” arrangement, in which one or both of electrodes24, 26 are unipolar electrodes referenced to the electrode on the pulsegenerator. The housing of implantable stimulator 12 may itself serve asa reference electrode for the active can arrangement. A variety ofpolarities and electrode arrangements may be used. Each lead 18, 20 maycarry a single electrode or an electrode array of multiple electrodes,permitting selection of different electrode combinations, includingdifferent electrodes in a given electrode array, and selection ofdifferent polarities among the leads for delivery of stimulation.

In addition to pulse width, as discussed above, the stimulation pulsesdelivered by implantable stimulator 12 are characterized by otherstimulation parameters such as a voltage or current amplitude and pulserate. Pulse width and the other stimulation parameters may be fixed,adjusted in response to sensed physiological conditions within or nearstomach 22, or adjusted in response to patient or physician inputentered via patient programmer 14. For example, in some embodiments,patient 16 may be permitted to adjust stimulation amplitude, pulsewidth, or pulse rate and turn stimulation ON and OFF via patientprogrammer 14.

Patient programmer 14 transmits instructions to stimulator 12 viawireless telemetry. Accordingly, stimulator 12 includes telemetryinterface electronics to communicate with patient programmer 14. Patientprogrammer 14 may be a small, battery-powered, portable device thataccompanies patient 16 throughout a daily routine. Patient programmer 14may have a simple user interface, such as a button or keypad, and adisplay or lights. Patient programmer also may include any of a varietyof audible, visual, graphical or tactile output media. Patientprogrammer 14 may be a hand-held device configured to permit activationof stimulation and adjustment of stimulation parameters.

Alternatively, patient programmer 14 may form part of a larger deviceincluding a more complete set of programming features including completeparameter modifications, firmware upgrades, data recovery, or batteryrecharging in the event stimulator 12 includes a rechargeable battery.Patient programmer 14 may be a patient programmer, a physicianprogrammer, or a patient monitor. In some embodiments, patientprogrammer 14 may be a general purpose device such as a cellulartelephone, a wristwatch, a personal digital assistant (PDA), or a pager.

Electrodes 24, 26 carried at the distal ends of lead 18, 20,respectively, may be attached to the wall of stomach 22 in a variety ofways. For example, the electrode may be formed as a gastric electrodethat is surgically sutured onto the outer wall of stomach 22 or fixed bypenetration of anchoring devices, such as hooks, needles, barbs orhelical structures, within the tissue of stomach 22. Also, surgicaladhesives may be used to attach the electrodes. In some cases, theelectrodes 24, 26 may be placed in the lesser curvature 23 on theserosal surface of stomach 22, within the muscle wall of the stomach, orwithin the mucosal or submucosal region of the stomach. Alternatively,or additionally, electrodes 24, 26 may be placed in the greatercurvature of stomach 22 such that stimulation is delivered to thegreater curvature.

In some embodiments, system 10 may include multiple stimulators 12 ormultiple leads 18, 20 to stimulate a variety of regions of stomach 22.Stimulation delivered by the multiple stimulators may be coordinated ina synchronized manner, or performed without communication betweenstimulators. Also, the electrodes may be located in a variety of siteson the stomach, or elsewhere in the gastrointestinal tract, dependent onthe particular therapy or the condition of patient 16. Stimulationdelivered by the multiple stimulators may be coordinated in asynchronized manner, or performed independently without communicationbetween stimulators. As an example, one stimulator may control otherstimulators by wireless telemetry, all stimulators may be controlled bypatient programmer 14, or the stimulators may act autonomously subjectto parameter adjustment or downloads from patient programmer 14.

FIG. 2 is a block diagram illustrating example components of astimulator 12 that delivers gastric stimulation therapy to patient 16.In the example of FIG. 2, stimulator 12 includes stimulation generator28, processor 30, memory 32, wireless telemetry interface 34 and powersource 36. In some embodiments, stimulator 12 may generally conform tothe Medtronic Itrel 3 Neurostimulator, manufactured and marketed byMedtronic, Inc., of Minneapolis, Minn. However, the structure, design,and functionality of stimulator 12 may be subject to wide variationwithout departing from the scope of the disclosure as broadly embodiedand described in this disclosure.

Processor 30 controls stimulation generator 28 by setting and adjustingstimulation parameters such as pulse amplitude, pulse rate, pulse widthand duty cycle, in the case that stimulation generator 28 generatespulses. Alternative embodiments may direct stimulation generator 28 togenerate continuous electrical signals, e.g., a sine wave. Processor 30may be responsive to parameter adjustments or parameter sets receivedfrom patient programmer 14 via telemetry interface 34. Hence, patientprogrammer 14 may program stimulator 12 with different sets of operatingparameters. In some embodiments, stimulation generator 28 may include aswitch matrix. Processor 30 may control the switch matrix to selectivelydeliver stimulation pulses from stimulation generator 28 to differentelectrodes 38 carried by one or more leads 18, 20 (FIG. 1). In someembodiments, stimulator 12 may deliver different stimulation programs topatient 16 on a time-interleaved basis with one another.

Memory 32 stores instructions for execution by processor 30, includingoperational commands and programmable parameter settings. Examplestorage areas of memory 32 may include instructions associated withtherapy programs 33 and anti-desensitization features 35. Programs 33may include each program used by stimulator 12 to define parameters andelectrode combinations for gastric stimulation therapy.Anti-desensitization features 35 may include instructions forapplication of one or more anti-desensitization features, as describedin this disclosure, such as when to start and stop a lockout period,therapy window durations, therapy schedules, burst pattern variationparameters, multi-site stimulation parameters, electrode selectionorders or functions, and burst pattern parameter selection instructions.

Processor 30 may access a clock or other timing device 29 withinstimulator 12 to determine pertinent times, e.g., for enforcement oftherapy schedules, lockout periods, and therapy windows, and maysynchronize such times with times maintained by patient programmer 14.Memory 32 may include one or more memory modules constructed, e.g., asrandom access memory (RAM), read-only memory (ROM), non-volatile randomaccess memory (NVRAM), electrically erasable programmable read-onlymemory (EEPROM), and/or FLASH memory. Processor 30 may access memory 32to retrieve instructions for control of stimulation generator 28 andtelemetry interface 34, and may store information in memory 32, such asoperational information.

Wireless telemetry in stimulator 12 may be accomplished by radiofrequency (RF) communication or proximal inductive interaction ofimplantable stimulator 12 with patient programmer 14 via telemetryinterface 34. Processor 30 controls telemetry interface 34 to exchangeinformation with patient programmer 14. Processor 30 may transmitoperational information and receive stimulation parameter adjustments orparameter sets via telemetry interface 34. Also, in some embodiments,stimulator 12 may communicate with other implanted devices, such asstimulators or sensors, via telemetry interface 34.

Power source 36 delivers operating power to the components ofimplantable stimulator 12. Power source 36 may include a battery and apower generation circuit to produce the operating power. In someembodiments, the battery may be rechargeable to allow extendedoperation. Recharging may be accomplished through proximal inductiveinteraction between an external charger and an inductive charging coilwithin implantable stimulator 12. In other embodiments, an externalinductive power supply may transcutaneously power implantable stimulator12 whenever stimulation therapy is to occur.

Implantable stimulator 12 is coupled to electrodes 38, which maycorrespond to electrodes 24 and 26 illustrated in FIG. 1, via one ormore leads 18, 20. Implantable stimulator 12 provides stimulationtherapy to the gastrointestinal tract of patient 16. Stimulationgenerator 28 includes suitable signal generation circuitry forgenerating a voltage or current waveform with a selected amplitude,pulse width, pulse rate, and duty cycle. In general, as described inthis disclosure, the electrical stimulation and stimulation pulsesgenerated by stimulation generator 28 may be formulated with pulsewidths and appropriate times suitable to cause substantial gastricdistention without excessive consumption of power provided by powersource 36.

In the example of FIGS. 1 and 2, stimulator 12 includes leads 18, 20. Inother embodiments, stimulator 12 may be a leadless stimulator, sometimesreferred to as a microstimulator, or combination of such stimulators. Inthis case, the housing of stimulator 12 may include multiple electrodesto form electrode combinations for delivery of stimulation to thestomach, intestines, or other organs within patient 16. In additionalembodiments, stimulator 12 may include three of more leads.

FIG. 3 is a block diagram illustrating example components of patientprogrammer 14 that receives patient input and communicates withstimulator 12. As shown in FIG. 3, patient programmer is an externalprogrammer that patient 16 uses to control the gastric stimulationtherapy delivered by stimulator 12. Patient programmer 14 includesprocessor 40, user interface 42, memory 44, telemetry interface 50 andpower source 52. In addition, processor 40 may access a clock or othertiming device 41 to adhere to lockout periods, therapy windows, andtherapy schedules, as applicable. Patient 16 may carry patientprogrammer 14 throughout therapy so that the patient can initiate, stopand/or adjust stimulation as needed.

While patient programmer 14 may be any type of computing device, thepatient programmer may preferably be a hand-held device with a displayand input mechanism associated with user interface 42 to allowinteraction between patient 16 and patient programmer 14. Patientprogrammer 14 may be similar to a clinician programmer used by aclinician to program stimulator 12. The clinician programmer may differfrom patient programmer by having additional features not offered topatient 16 for security, performance, or complexity reasons.

User interface 42 may include display and keypad (not shown), and mayalso include a touch screen or peripheral pointing devices. Userinterface 42 may be designed to receive an indication from patient 16 todeliver gastric stimulation therapy. The indication may be in the formof a patient input in the form of pressing a button representing thestart of therapy or selecting an icon from a touch screen, for example.In alternative examples, user interface 42 may receive an audio cue frompatient 16, e.g., the patient speaks to a microphone in order to performfunctions such as beginning stimulation therapy. Patient programmer 14acts as an intermediary for patient 16 to communicate with stimulator 12for the duration of therapy.

User interface 42 may provide patient 16 with information pertaining,for example, to the status of an indication or a gastric stimulationfunction. Upon receiving the indication to start stimulation, userinterface 42 may present a confirmation message to patient 16 thatindicates stimulation has begun. The confirmation message may be apicture, icon, text message, sound, vibration, or other indication thatcommunicates the therapy status to patient 16. User interface 42 alsomay provide the status of an anti-desensitization feature to patient 16.For example, user interface 42 may indicate that the lockout period iscurrently active, e.g., with a small lock symbol displayed on thescreen, or that a therapy window is about to expire.

In addition, user interface 42 may present information relating to thetherapy schedule or therapy windows. In some cases, user interface 42may prompt the patient 16 to initiate stimulation when a permitted timeperiod on the therapy schedule has arrived. Alternatively, userinterface 42 may display a lockout message pop up window to patient 16if the user interface receives an indication from patient 16 to delivertherapy during the lockout period. In any case, user interface 42 maynotify patient 16 when request indicated by patient input has beencompleted or cannot be completed due to a restriction.

Processor 40 may include one or more processors such as amicroprocessor, a controller, a DSP, an ASIC, an FPGA, discrete logiccircuitry, or the like. Processor 40 may control information displayedon user interface 42 and perform certain functions when requested bypatient 16 via input to the user interface. Processor 40 may retrievedata from and/or store data in memory 44 in order to perform thefunctions of patient programmer 14 described herein. For example,processor 40 may generate a selection of electrodes as ananti-desensitization feature based upon instructions stored in memory44, and processor 40 may then store the selection in memory 44.

Memory 44 may include programs 46 that are stimulation programs used todefine therapy delivered to patient 16. When a new program is requestedby stimulator 12 or patient 16, one of programs 46 may be retrieved frommemory 44 and transmitted to stimulator 12 in order adjust the gastricstimulation therapy. Alternatively, patient 16 may generate a newprogram during therapy and store it with programs 46. Memory 44 maystore instructions relating to anti-desensitization features 48, whichmay include instructions relating to the lockout period, therapy window,therapy schedule, burst pattern parameter selection, a burst patternvariation, and/or multi-site features. For the lockout period, forexample, such instructions may define the duration of the lockoutperiod, when to start and stop the lockout period, or any otherparameters that may define the lockout period. Memory 44 may include anyvolatile, non-volatile, fixed, removable, magnetic, optical, orelectrical media, such as a RAM, ROM, CD-ROM, hard disk, removablemagnetic disk, memory cards or sticks, NVRAM, EEPROM, flash memory, andthe like.

While patient programmer 14 is generally described as a hand-heldcomputing device, the patient programmer may be a notebook computer, acell phone, or a workstation, for example. In some embodiments, patientprogrammer 14 may comprise two or more separate devices that perform thefunctions ascribed to the patient programmer. For example, patient 16may carry a key fob that is only used to start or stop stimulationtherapy. The key fob may then be connected to a larger computing devicehaving a screen via a wired or wireless connection when informationbetween the two needs to be synchronized. Alternatively, patientprogrammer 14 may simply be small device having one button, e.g., asingle “start” button, that only allows patient 16 to start stimulationtherapy when the patient feels hungry or is about to eat.

Stimulator 12 may store and implement any of the anti-desensitizationfeatures, such as the lockout period, the therapy window, and theselection of electrodes. When patient 16 presses the single start buttonto start stimulation again, the stimulation delivery may be subject tothe anti-desensitization features, such as the lockout period, therapywindow, and/or therapy schedule. In addition, in applying stimulation,programmer 14 and/or stimulator 12 may apply other anti-desensitizationfeatures, such as the burst pattern parameter selection, multi-site,and/or burst pattern variation features. Hence, in some embodiments,programmer 14 may have only a single start button that is accessible tothe patient to attempt to activate stimulation, subject to one or moreapplicable anti-desensitization features that may control when or howstimulation is applied.

FIG. 4 is a conceptual diagram illustrating example electrode arrays 54and 56 positioned on stomach 22 of patent 16. As shown in FIG. 4,electrode arrays 54 and 56 are attached to the outside of stomach 22.Electrode array 54 includes five discrete electrodes 54A, 54B, 54C, 54Dand 54E (collectively “electrodes 54”) and electrode array 56 includesfive discrete electrodes 56A, 56B, 56C, 56D and 56E (collectively“electrodes 56”). Electrode arrays 54 and 56 are positioned along lessercurvature 23 of stomach 22, but the electrode arrays may be positionedanywhere upon stomach 22 as desired by the clinician. In addition, oneor both electrode arrays 54 may be positioned at different sites, suchas on the duodenum or elsewhere along the small intestine.

Electrode arrays 54 and 56 are provided in place of electrodes 24 and 26of FIG. 1. In this manner, electrode arrays 54 and 56 may be used aspart of a multi-site anti-desensitization feature to distributeelectrical stimulation energy among a larger number of varied tissuesites, instead of concentrating stimulation at a single tissue site overan extended period of time. For example, electrode arrays 54, 56 may beused to support selection of different electrode combinations associatedwith different positions, or tissue sites, on a gastrointestinal organsuch as the stomach. Each electrode array 54, 56 may include a pluralityof electrodes, e.g., electrodes 54A-54E and electrodes 56A-56E, that maybe individually selected to form a variety of electrode combinationsthat distribute electrical stimulation therapy to different therapysites. Electrode combinations may include selected electrodes ondifferent leads or the same lead. For example, an electrode combinationmay combine electrodes from array 54, array 56, or both array 54 and 56,as well as electrodes from other arrays, if provided. In general,electrodes in arrays 54, 54 may be positioned to form electrodecombinations at tissue sites separated by greater than approximately 1cm, greater than approximately 3 cm, or greater than approximately 5 cm.The distribution of stimulation among electrode combinations atdifferent tissue sites may help to reduce desensitization and therebyextend the efficacy of electrical stimulation without compromisingpatient treatment.

In the example of FIG. 4, electrode arrays 54 and 56 and electrodes54A-54E and 56A-56E may not necessarily be sized in proportion tostomach 22. For example, electrode arrays 54 and 56 may be configured tobe a smaller size so that the electrodes can be packed into a smallerarea of stomach 22. Alternatively, electrode arrays 54 and 56 and theircorresponding electrodes may differ in size on stomach 22. For example,electrodes in array 54 may each have a larger surface area than each ofthe electrodes in array 56. In addition, electrodes 54 may havediffering surface areas between each of the electrodes. In this manner,varying electrode surface area may act as an additionalanti-desensitization feature to slightly alter the stimulation therapyover time.

Stimulator 12 may deliver electrical stimulation to stomach 22 using oneor more electrodes of electrode arrays 54 and 56. Each of the electrodesin arrays 54, 56 may be coupled to stimulator 12 via a respectiveelectrical conductor within leads 18, 20, and may be individuallyselectable. Each lead 18, 20 may include multiple conductors, each ofwhich is coupled at a distal end to one of the electrodes in arespective electrode array 54, 56 and at the proximal end to a terminalof a switch device by which stimulator 12 directs stimulation energy toselected electrodes, e.g., as anodes or cathodes. In some examples, asmentioned above, stimulator 12 may deliver stimulation using oneelectrode from each of electrode arrays 54 and 56, multiple electrodesfrom one array and a single electrode from another array, or multipleelectrodes in a single array.

Stimulator 12 may cycle through or randomly select different electrodesfrom each of electrode arrays 54 and 56 to produce different electrodecombinations to vary the stimulation tissue sites throughout therapy. Inother examples, stimulator 12 may deliver stimulation using acombination of any electrodes from only electrode array 54, onlyelectrode array 56, or a combination of electrodes from electrode arrays54 and 56. In alternative examples, the housing of stimulator 12 mayalso be used as an electrode. The housing of stimulator 12 may bereferred to as a can electrode, return electrode, or active canelectrode, as mentioned above.

While electrode arrays 54 and 56 are shown as each having fiveelectrodes, electrode arrays 54 and 56 may have any number of electrodesdesired by the clinician or necessary for efficacious therapy. Electrodearrays 54 and 56 may have differing numbers of electrodes, andstimulator 12 may be connected to a different number of electrodearrays, such as only one array or more than three arrays. In addition,electrode arrays 54 and 56 may have corresponding electrodes configuredin a different orientation than the linear orientation shown in FIG. 4.For example, electrode arrays 54 and 56 may have electrodes oriented ina circular pattern, rectangular grid pattern, curved pattern, starpattern, or another pattern that may enhance the anti-desensitizationfeature of electrode arrays 54 and 56.

At some time during therapy, it is possible that one or more ofelectrodes 54 and 56 may no longer be functional due to a broken lead,broken conductor, disconnected circuit, corroded electrode, or someother problem. Stimulator 12 may recognize a dysfunctional electrodeduring an electrode integrity check at various times during therapy.Once an electrode is determined to be dysfunctional, stimulator 12 mayremove that electrode from the possible electrodes for therapy.Stimulator 12 may also alter the algorithm used for generating aselection of electrodes for delivering therapy to ensure that onlyfunctional electrodes are included in the selection. In some examples,the clinician may manually alter the selection of electrodes when anelectrode is determined to be dysfunctional.

In general, multiple electrodes implanted at multiple tissue sites, asshown in FIG. 4, may permit stimulation to be delivered to differentstimulation sites at different times. For example, stimulation havingsubstantially similar parameters or different parameters may be appliedto different tissue sites during different therapy windows or therapyschedule time periods such that different tissue sites are stimulated toprevent or delay desensitization. The stimulation parameters may beselected to achieve similar therapeutic effects, e.g., gastricdistention, even though the stimulating is delivered to different tissuesites.

Also, in some embodiments, stimulation may be delivered to differentstimulation sites during the same therapy schedule periods or therapywindows. For example, therapy can be adjusted during the course ofstimulation to use different electrode combinations and associatedtissue sites. In addition, in other embodiments, a multi-site featuremay be applied such that stimulation is delivered simultaneously or onan alternating, time-interleaved basis, e.g., pulse by pulse or burst byburst or burst pattern by burst pattern, to different electrodecombinations and different associated tissue sites.

With reference to FIG. 4, for example, one pulse or burst could beapplied to an electrode combination via array 54 while the next pulse orburst or burst pattern could be applied to an electrode combination viaarray 56. In this manner, a single tissue site is stimulated less often.Yet, the stimulation delivered to different tissue sites on analternating basis may still achieve a substantially identical desiredoverall therapeutic effect, e.g., gastric distention, nausea ordiscomfort in the case of obesity.

Stimulator 12 may deliver first electrical stimulation therapy via afirst electrode combination associated with a first position on thegastrointestinal organ for a first period of time, and deliver secondelectrical stimulation therapy to the gastrointestinal organ via asecond electrode combination associated with a second position on thegastrointestinal organ for a second period of time. The stimulationtherapies may comprises pulses, pulse trains, pulse bursts, burstpatterns, or other patterns, and may include various duty cycles.Accordingly, the first and second period of time may generally refer toa period of time during which stimulation is actively delivered via agiven electrode combination, even though stimulation may be delivered indifferent forms. Again, the first and second electrical stimulationtherapies are configured to produce a substantially identicaltherapeutic result. In some cases, the first and second periods of timemay be the same or different, and may partially overlap or not overlapwith one another. If the first and second periods of time do notoverlap, they may be separated by a gap in time or be arranged such thatthe second period of time commences immediately upon termination of thefirst period of time. In addition, the first and second periods of timemay be greater than or equal to thirty seconds, greater than or equal toone minute, greater than or equal to five minutes, greater than or equalto ten minutes, greater than or equal to one hour, or greater than orequal to one day.

Again, delivery of the first and second gastric electrical stimulationtherapy may be time-interleaved or time-independent. For example,different pulses or bursts of pulses or burst patterns may be deliveredvia electrode combinations at different positions on a time-alternatingbasis within a given therapy period or therapy window. Alternatively,different therapy periods or therapy windows may use different electrodecombinations at different positions on a time-independent basis. In thislatter case, instead of alternating between different positions,delivery of stimulation is generally time-independent in thatstimulation may be delivered at a single given position forsubstantially an entire therapy period or window. Then, in a subsequenttherapy period or window, stimulation may be delivered at a different,single given position for substantially the entire subsequent therapyperiod or window. In this case, delivery of stimulation istime-independent in the sense that there is no alternating of therapy atdifferent positions within a given therapy period or window.

In summary, different electrode sets implanted at different locations onan applicable gastrointestinal organ, such as the stomach, may be usedin different therapy periods, e.g., hours, or days, at different timeswithin a given therapy period, or on alternating multi-channel,multi-site basis. Also, electrodes in one array 54 may be used for anextended period of time such as several seconds, minutes, hours, days orweeks, followed by transition to electrodes on the other array 56 afterthe extended period of time. In some cases, delivery of stimulation toone electrode set may at least partially overlap with delivery ofstimulation to the other set of electrodes. However, at least portionsof the stimulation delivered to the first and second electrode sets maynot overlap. In other words, the first period of time for whichstimulation is delivered to the first electrode set may either partiallyoverlap or not overlap with the first period of time for whichstimulation is delivered to the second electrode set. In each case, thestimulation delivered via the various electrodes is configured tosupport substantially the same therapeutic effect, such as gastricdistension. Yet, the first and second electrode sets are displaced fromone another by a sufficient distance so that different tissue sitesreceive the stimulation. As examples, electrodes in array 54 may bedisplaced from electrodes in array 56 by at least approximately 1 cm,more preferably at least approximately 3 cm, and still more preferablyat least approximately 5 cm.

FIG. 5A is an example timing diagram illustrating a continuous train 59of pulses that may be used in electrical stimulation delivered topatient 12. FIGS. 5B, 5C and 5D are example timing diagrams illustratingbursts of pulses that may be delivered as burst patterns in theelectrical stimulation delivered to patient 16. As shown in FIG. 5B,electrical pulses generated by stimulator 12 may be delivered to patient16 in bursts of pulses, where each pulse includes n pulses, and n isgreater than one. The pattern of bursts may be a regular pattern or anirregular pattern. In addition, as shown in FIG. 5B, a burst patterncomprises multiple pulse bursts. FIG. 5C illustrates delivery of singleburst patterns that generally conform to therapy windows. FIG. 5Dillustrates delivery of multiple burst patterns within given therapywindows.

Each burst 62 includes multiple electrical pulses. In the example ofFIG. 5B, T_(on) is the time that stimulator 12 delivers continuouspulses that make up each burst 62, while T_(off) is the time stimulator12 is not delivering pulses between each burst 62. The ratio of T_(on)to T_(off) is the duty cycle of burst pattern 60 that is set by theclinician to provide effective therapy. The duty cycle of burst pattern60 may be set anywhere between 0% and 100% ON. However, generally theduty cycle may be less than 50% ON and more than 50% OFF. Hence, acontinuous train of pulses can be gated ON to form a pulse burst.Likewise, a series of pulse bursts may be gated ON to form a burstpattern 60 containing multiple pulse bursts 62. Stimulation may bedelivered, in various embodiments, as pulses, bursts, burst patterns,continuous pulse trains, or the like.

While FIG. 5B illustrates each burst 62 having eight pulses and burstpattern 60 having seven bursts for purposes of illustration, any numberof pulses and bursts 62 may define one burst pattern 60. For example,burst pattern 60 may include over one hundred bursts while each burst 62may include more than 20 pulses. Alternatively, burst pattern 60 mayinclude fewer bursts 62 with each burst having fewer pulses. A clinicianmay program stimulator 12 to deliver burst pattern 60 to patient 16 withthe desired number of bursts 62 and pulses to treat patient 16. Thepulses of bursts 62 and each of the bursts may be delivered according toexample stimulation parameters described herein.

FIG. 5C illustrates an example therapy schedule time period P thatincludes multiple therapy applications within therapy windows W. Hence,one or more therapy windows W may be applied during a therapy scheduletime period P. For example, period P may be equal to a 24 hour day ofpatient 16, e.g., from midnight to midnight. In the examples of FIGS. 5Cand 5D, the lockout period L prevents stimulator 12 from deliveringstimulation within a predetermined period of time following terminationof stimulation. In this manner, lockout period L, whether maintained bystimulator 12 or patient programmer 14, functions as ananti-desensitization feature by preventing continuous or excessivedelivery of stimulation. Instead, stimulation is generally deliveredwhen needed, rather than at times when the stimulation is not necessary,such as between meals or while the patient is sleeping. In addition,stimulator 12 and/or patient programmer 14 may implement additionalanti-desensitization features in the form of therapy windows and atherapy schedule.

As shown in FIGS. 5C and 5D, delivery of therapy may be permitted onlyduring schedule times S permitted by a therapy schedule. Times S may besubstantially coincident with meal times and, optionally, snack times.Each time S may extend over a period of time in which it is likely thatthe patient may ingest a meal. For breakfast, for example, the time Smay run from 6 am to 8 am. As mentioned previously, times S on thetherapy schedule may have start and/or end times and/or durations thatvary from day to day, as another anti-desensitization feature. Iftherapy is requested during a schedule time S, then therapy may bedelivered, e.g., by transmission of a command from patient programmer 14to stimulator 12, subject to other anti-desensitization features. Iftherapy is requested outside of one of the schedule times S, however,than delivery of therapy is not permitted, either by refusal ofprogrammer 14 to transmit a request or refusal of stimulator 12 todeliver stimulation in response to a request from the programmer.

With further reference to FIG. 5C, a therapy window W specifies amaximum time for which therapy may be delivered. In this manner, thetherapy window W limits the duration for which stimulation is deliveredat a given time. As mentioned previously, the therapy window W mayselected based on a first period of time that is found to be sufficientto cause a desired physiological response or therapeutic result for asecond period of time. The second period of time may be greater than orless than the first period of time, but extends at least in part beyondthe end of the first period of time. The first period of time may beselected to produce the desired therapeutic effect for the second periodof time and, in some cases, may be the minimum period of time sufficientto produce the desired therapeutic effect for the second period of time.

In the case of gastric distention, for example, the desired therapeuticeffect, response or result may be a maintenance of an increase ingastric volume at a threshold percentage of a target level, e.g., a 50%volume increase above a baseline level of gastric volume. Programmer 14and/or stimulator 12 may start a clock or other timing device uponinitiation of delivery of therapy and then require termination oftherapy prior to expiration of an applicable therapy window W, whichcorresponds to the first period of time sufficient to produce thedesired therapeutic effect for the second period of time. In thismanner, any single administration of therapy is limited in time by thetherapy window W in order to reduce the likelihood of desensitization,and possibly conserve power resources. As described above, the therapywindow W may be selected to be the approximately the minimum timenecessary to achieve a desired therapeutic effect for a desired periodof time, i.e., the second period of time, given a set of stimulationparameters and/or other factors.

Alternatively, the therapy window W may be approximately this minimumtime plus an optional margin such that the therapy window W is somewhatgreater than or equal to the minimum. In any event, the therapy windowis a function of an approximate duration of the gastric electricalstimulation therapy that is effective in producing a desired therapeuticeffect for a desired period of time during and after termination of thegastric electrical stimulation therapy. Notably, the therapy window maybe shorter than the desired period of time for which the therapeuticresult is produced because the recovery time of the tissue may permitthe therapeutic result to be prolonged to a desired degree for anextended period of time following termination of delivery ofstimulation.

The length of the therapy window W, like the lockout period L andscheduled time S may be the same throughout the day, or may vary fordifferent meals. For example, a patient 16 may desire a longer scheduletime S for dinner, to permit flexible dinner planning. Also, the therapywindow W may be increased for some meals, such as dinner, which may havea more leisurely pace to provide an extended period in which the desiredtherapeutic effect is available. If therapy starts within a scheduletime S, the therapy may be permitted to extend beyond the schedule timeS, subject to the maximum time specified by the therapy window W.Alternatively, therapy may be terminated at the end of the scheduledtime S if it would extend beyond the scheduled time S.

In some embodiments, each therapy application within a therapy window Wmay contain one or more burst patterns 60 containing multiple bursts 62.A single burst pattern 60 may reside within each therapy window W andform the therapy application for a particular therapy schedule timeperiod S. Alternatively, a therapy window W may include multiple burstpatterns 60, e.g., as shown in FIG. 5D. Each time that therapy isdelivered to patient 16, stimulator 12 delivers bursts of pulses asdescribed above for burst pattern 60.

The beginning of each therapy application in a therapy window W may berelated to when patient 16 eats a meal, and may be either initiated bypatient 16 or scheduled by stimulator 12. When initiated by a patient,delivery of the therapy is permitted within a permitted time S, per thetherapy schedule. The therapy may be initiated at any time within thetime S, and need not be at the beginning of the time S. Once started,however, the therapy generally is limited to the duration of anapplicable therapy window W, e.g., to avoid or reduce desensitizationand/or conserve power.

As shown in FIG. 5C, stimulator 12 delivers therapy to patient 16 duringtimes T₂, T₄ and T₆. During times T₁, T₃, T₅, and T₇, no electricalstimulation is delivered to patient 16. At the end of each therapyapplication, which is coincident with a therapy window W, system 10implements lockout period L to prevent stimulator 12 from deliveringtherapy to patient 16 until lockout period L has elapsed, either bydirectly locking out stimulator 12 from delivery therapy or locking outpatient programmer 14 from transmitting a command to initiate deliveryof therapy during the lockout period. In addition, after the end of eachtherapy window W, a desired therapeutic effect may remain in effect forsome time.

Therapy windows W and burst patterns 60 may be substantially equivalentwith one another throughout period P or different. Likewise, lockoutperiods L may be substantially equivalent throughout period P ordifferent. As an alternative, in some cases, therapy windows W and burstpatterns 60 may change in timing and/or duration. For example, timingand/or duration of burst patterns 60 may change depending upon the timeof day the therapy is started. If multiple burst patterns, eachcontaining multiple pulse bursts, are delivered within an applicabletherapy window, the timing between successive burst patterns may befixed or variable. If the timing is variable, the time between burstpatterns may be the same throughout a given burst pattern.Alternatively, the times between different burst patterns in a givenwindow W may vary. In addition, the duration of burst patterns deliveredto the patient may vary among different therapy windows, or within agiven therapy window. Also, the durations of burst patterns may varyamong different therapy windows, or within a given therapy window.

As an illustration, for purposes of example and without limitation, aparticular therapy window could include x burst patterns. Each burstpattern could include y pulse bursts. Each pulse burst could include zpulses. Each burst pattern could have a duration of time t₁, and beseparated in time by time t₂. In operation, the number x of burstpatterns could be varied from therapy window to therapy window. Thenumber of bursts y and pulses in each burst z could likewise be varied.In addition, the times t₁ and t₂ could be varied from therapy window totherapy window or within a given therapy window such that some burstpatterns in a window have different durations, and such that the timebetween successive burst patterns in a window is different.

FIG. 5D shows multiple burst patterns provided in successive therapywindows. For example, four burst patterns 60A of equal duration andequal time spacing between successive burst patterns are provided in afirst therapy window W at time T₂. Three burst patterns 60B of differentdurations and different time spacing are provided in the next therapywindow W at time T₄. Four burst patterns 60C of equal duration butdifferent time spacing are provided in the therapy window W at time T₆.Hence, multiple types of variation may be introduced into the burstpatterns to provide further variation that may prevent or delaydesensitization of stimulated tissue in patient 16.

With further reference to FIGS. 5C and 5D, lockout period L may also bevary, e.g., as a function of the time of day. For example, lockoutperiods L may be shorter in duration during the morning while lockoutperiods L in the evening may be longer to prevent patient 16 fromsleeping with undigested food in stomach 22. In addition, times betweensuccessive therapy applications may vary due to when patient 16 eats. Asshown in FIG. 5C, time T₅ is greater than times T₁, T₃ and T₇. In otherexamples, period P may include more or less than three burstapplications, as needed by patient 16 and allowed by the clinician.

FIG. 5E shows delivery of various burst patterns throughout a period P.Whether lockout periods L, schedule times S, and therapy windows W areused or not, FIG. 5E illustrates delivery of stimulation using burstpatterns that may vary in number, duration and/or timing from period toperiod P. In a first period P, for example, burst patterns may bedelivered as indicated by 60D, 60F and 60H. In a second period P, burstpatterns may be delivered as indicated by 60E, 60G, 601, and 60J. Asshown in FIG. 5D, the burst patterns may be delivered with differentstart times and durations. In addition, the number of burst patterns mayvary from period to period, e.g., as shown by burst pattern 60J.

Although a relatively small number of burst patterns are shown in FIG.5E, a much larger number of burst patterns may be delivered. As oneexample, programmer 14 and/or stimulator 12 may be configured to deliverburst patterns having durations of 1 to 60 minutes, with a number ofburst patterns per 24-hour period being variable from 1 to 100 burstpatterns. By varying the timing, duration and number of burst patternsfrom period to period, desensitization can be prevented or delayed. Inaddition, desensitization can be prevented or delayed by deliveringmultiple burst patterns at different times and with different durationswithin a given period. In some embodiments, the number, timing andduration of burst patterns may be specified by a clinician or permittedto vary automatically, e.g., randomly, within limits specified by theclinician via a physician programmer, according to a randomizationalgorithm or other algorithm used by programmer 14 and/or stimulator 12.

FIG. 5F is a graph illustrating gastric distention during and followingapplication of stimulation within a therapy window. The graph of FIG. 5Fis provided for purposes of illustration and depicts the concept of atherapy window and associated gastric distention response. Accordingly,FIG. 5F does not represent actual data and is not drawn to scale. In theexample of FIG. 5, stimulation is delivered for a first period of timeT1=t4-t1, consistent with a therapy window. In particular, following aninitial time t0, stimulation is delivered at time t1 and maintaineduntil time t4 During stimulation, gastric volume increases, and reachesa therapeutic threshold (defined here as a gastric volume that is 50%greater than gastric volume at baseline t0) at time t2, and at a latertime t3, reaches a maximum level.

Delivery of stimulation may continue until time t4. When stimulation isterminated at time t4, gastric volume gradually decreases, reaching thethreshold for therapeutic efficacy (the therapeutic threshold) at timet5. By time t6, gastric volume has decayed back to baseline levelsobtained at t0. Thus, by applying stimulation for a time T1, gastricvolume is increased over baseline levels to a therapeutic range for atime T2. As the time for increasing gastric volume after the onset ofstimulation is generally greater than the time for gastric volume toreturn to baseline levels after termination of stimulation, T2 willgenerally be greater than T1.

Note that, in this discussion, gastric volume is used as an example of ameasure of muscle tone. Other terminology may also be usedinterchangeably including gastric distention, gastric tone, gastricvolume, gastric relaxation. Other measures of gastric relaxation mayinclude changes in length of any segment of the stomach, or thethickness of the stomach muscle wall, as measured by ultrasound,magnetic, mechanical, optical, or other electronic transducers;

In the example of FIG. 5F, the gastric stimulation produces an increasein gastric volume relative to an initial volume prior to stimulation.After stimulation is stopped at time t4, the gastric volume does notimmediately return to the initial volume. Rather, gastric volume decayssomewhat slowly such that gastric volume remains above the targetthreshold level (i.e., a volume that is 50%≧baseline volume) achieved bystimulation until time t5. If the desired therapeutic effect occurs whengastric volume remains above the target threshold level (i.e., gastricvolume remains ≧50% above baseline gastric volume), then the desiredtherapeutic effect persists for an additional time t5-t4 followingcessation of stimulation. Hence, stimulation for a first period of timeT1=t3-t1 can produce a desired therapeutic effect for a second period oftime T2=t5-t2, wherein T2 is greater than T1.

FIGS. 6A, 6B and 6C are example timing diagrams illustrating continuouspulses and bursts of pulses delivered to patient 16 when system 10delivers therapy to multiple distinct sites, i.e., via multiple,different physical channels, as part of a multi-siteanti-desensitization feature. Such channels may be realized by differentelectrodes and associated conductors within leads 18, 20 that can beselected to deliver therapy. Channels 1 and 2 will be described hereinas example channels that deliver stimulation therapy. Channels 1 and 2may both indicate stimulation delivered to the same organ such asstomach 22 or the small intestine via respective electrode combinations.The small intestine may be stimulated, e.g., at the duodenum or thejejunum, for example. The stomach may be stimulated, e.g., in the lesseror greater curvature.

FIG. 6A illustrates a timing diagram for two channels, channel 1 andchannel 2. Channels 1 and 2 deliver stimulation to a different electrodecombinations. In the example of FIG. 6A, channel 1 delivers bursts 66 ofdiscrete pulses over time while channel 2 delivers a continuous train ofpulses. Pulses delivered by channel 1 and channel 2 may have the sameparameters or different parameters, depending upon the tissue treated bychannels 1 and 2, and may be delivered together within the same therapywindow. However, the stimulation delivered via channel 1 and channel 2is selected to produce substantially the same therapeutic effect.

FIG. 6B shows bursts 68 of pulses on channel 1 and bursts 70 of pulseson channel 2 for multi-site gastric stimulation. Pulse bursts 68 and 70are shown in synchronous burst mode such that bursts 68 and 70 haveequivalent duty cycles. Bursts 68 and 70 are offset from each other intime, such that they are delivered on an alternating basis, but thebursts may also be delivered at the same time in some exampleembodiments. Bursts 68 and 70 are delivered during the ON portion of theduty cycle. Pulse bursts 68 and 70 may be delivered in a variety ofdifferent modes, such as a continuous mode, an asynchronous burst mode,or a synchronous burst mode. In a continuous mode, the pulse train isdelivered relatively continuously over an active period in whichstimulation is “ON.” In an asynchronous burst mode, the pulse train isdelivered in periodic bursts during the active period. The continuousand asynchronous burst modes do not rely on synchronization betweenchannels 1 and 2.

In a synchronous burst mode, the pulse train is delivered in bursts thatare synchronized with multiple channels, such as channels 1 and 2. Inthis sense, the synchronous burst mode may be viewed as a closed loopapproach. Stimulator 12 may synchronize electrical stimulation betweenchannels 1 and 2 in order for the resulting organ response tostimulation to be matched for maximal efficacy. Channels 1 and 2 mayactivate stimulation to cause gastric distention and thereby discouragethe intake of excessive amounts of food. In the example of FIG. 6B, thealternating bursts may be delivered on a time-interleaved basis withinthe same therapy window. The duration of each burst may be greater thanor equal to approximately thirty seconds. By shifting between differentelectrode combinations on a time-interleaved basis, a multi-sitestimulation feature may reduce tissue desensitization.

FIG. 6C illustrates alternating burst patterns 72 and 74 betweendifferent electrode combinations on channels 1 and 2. Each of burstpatterns 72 and 74 includes multiple bursts of electrical pulses, e.g.,like bursts 68 or 70 of FIG. 6B. The alternating burst patterns 72, 74may be delivered on a time-interleaved basis within the same therapywindow. Burst patterns 72 and 74 may be referred to as alternatingsynchronous burst patterns because stimulator 12 only delivers one ofburst patterns 72 and 74 at any given time. In some examples, bursts 72and 74 may be provided such that the burst patterns on channels 1 and 2overlap or are separated by a certain interval. The duration of eachburst pattern may be greater than or equal to approximately thirtyseconds.

Hence, FIG. 6A shows channel 1 delivering pulse bursts and channel 2delivering continuous pulses, FIG. 6B shows synchronous delivery ofpulse bursts on an alternating basis between channel 1 and channel 2,and FIG. 6C shows synchronous delivery of burst patterns, eachcontaining multiple pulse bursts, on an alternating basis betweenchannel 1 and channel 2. In each case, stimulator 12 may use multi-citestimulation on channel 1 and channel 2 as an anti-desensitizationfeature to prevent or delay sensitization of a tissue site. The pulses,bursts, or burst patterns may be delivered to different electrodecombinations at different times to reduce desensitization.

With multi-site stimulation, stimulator 12 may deliver essentially thesame type of stimulation to achieve essentially the same type oftherapeutic effect via two or more different physical channels (i.e.,two different electrode combinations) to two different stimulation siteswith the same or similar stimulation parameters. As an example,stimulator 12 may deliver stimulation with similar parameters to twodifferent tissue sites on an alternating basis. The parameters may beselected such that the stimulation of the different tissue sites, whilepreventing or delaying desensitization, produce a desired overalltherapeutic effect, such as gastric distension or regulation ofmotility.

Stimulation parameters may be identical or differ slightly forelectrodes stimulating different tissue sites. In either case, however,it is desirable that the parameters of stimulation delivered on channels1 and 2 be selected to achieve substantially the same therapeuticeffect. If gastric distention is desired, for example, then stimulationparameters on channels 1 and 2 may be selected to support gastricdistention, and preferably similar amounts of gastric distention.

Although two channels are described for purposes of illustration,stimulator 12 may apply stimulation via three, four or more channels formulti-site stimulation to achieve similar therapeutic effects. Forexample, stimulator 12 may be coupled to multiple leads to deliverstimulation to different electrodes on the multiple leads.Alternatively, stimulator 12 may select multiple electrode combinationsavailable using electrodes deployed on a single implantable lead.

Stimulator 12 also may distribute pulsed stimulation therapy to at leastone of multiple tissue sites, e.g., via channels 1 and 2, in order toprovide another anti-desensitization feature to patient 16. Delivery ofpulse bursts or burst patterns to multiple stimulation sites on analternating basis may be preferred so that none of the stimulation sitesreceives continuous stimulation. Instead of providing substantiallycontinuous electrical pulses to stomach 22 via one channel, stimulator12 may spread out the electrical stimulation to multiple tissue sitesvia channels 1 and 2, where each channel includes electrodes positionedat different tissue sites. The resulting therapy may be effective incausing gastric distention or other desired effects, but prevents ordelays desensitization of the tissue that could otherwise result fromdelivering continuous pulses to the same tissue site on a persistentbasis. Instead, the tissue site receives stimulation intermittently,according to any of the multi-channel pulse or burst approachesillustrated in FIGS. 6A-6C.

FIGS. 7A, 7B, 7C, 7D, and 7E are example timing diagrams illustratingrelative timing of stimulation delivered via different channels inassociation with a multi-site stimulation feature. In the examples ofFIGS. 7A-7E, first, second and third channels deliver first, second andthird electrical stimulation therapy to a gastrointestinal organ viafirst, second and third electrode combinations, respectively. The first,second and third electrode combinations are associated with first,second and third positions on the gastrointestinal organs. The first,second and third stimulation therapy are delivered for first, second andthird periods of time, respectively, where each period of time isgreater than approximately thirty seconds, greater than or equal to oneminute, greater than or equal to five minutes, greater than or equal toten minutes, greater than or equal to one hour, or greater than or equalto one day. The first, second and third stimulation therapies areconfigured to produce a substantially identical therapeutic result, suchas distention. The first, second, and third period of time may partiallyoverlap or not overlap, and may be same or different durations.

As shown in FIG. 7A, first, second and third stimulation therapies 75,77, 79 may be delivered on Channels 1, 2, and 3, respectively, toselected electrode combinations, e.g., as pulses, bursts, burstpatterns, or continuous pulse trains. In the example of FIG. 7A, thestimulation 75, 77, 79 on each channel is ordered such that firststimulation 75 on Channel 1 is delivered for a first period of time t1,second stimulation 77 is then delivered for a second period of time t2after the first stimulation is stopped, and third stimulation 79 is thendelivered for a third period of time t3 after the second stimulation isstopped. In this example, the stimulations on Channels 1, 2 and 3 do notoverlap. Instead, stimulation on one channel starts upon cessation ofstimulation on another channel. However, overlapped stimulation may beused in other embodiments. Also, in FIG. 7A, stimulation one channelstarts immediately upon cessation of stimulation on the previouschannel. In other embodiments, however, a time gap may be providedbetween successive stimulations on different channels.

In FIG. 7A, stimulation is ordered such to apply first stimulation 75 onChannel 1, followed by second stimulation 77 on Channel 2, followed bythird stimulation 79 on Channel 3. In the example of FIG. 7B, however,the order is changed to apply first stimulation 75 on Channel 1,followed by third stimulation 79 on Channel 3, followed by secondstimulation on Channel 2. The order may be fixed or varying and may beselected by a physician. In some cases, a randomization orpseudo-randomization function may be applied to select the ordering ofthe Channels. In each case, the stimulation delivered on each channelmay be greater than approximately thirty seconds.

The positioning of the electrode combinations associated with Channels1, 2 and 3 may be unrelated to the ordering. For example, in some cases,the first, second and third positions may be arranged such that thefirst position is most proximal on the gastrointestinal organ, the thirdposition is most distal on the gastrointestinal organ, and the secondposition is between the first and third positions, yet stimulation neednot be applied along a particular axis relative to the gastrointestinalorgan. In general, there are no restrictions on alignment or orientationof different electrodes with respect to the GI tract. In particular, theelectrodes do not need to be positioned or aligned to produce afunctional peristaltic activity. The stimulation ordering andpositioning of the multiple electrode combinations may be flexible.Accordingly, the ordering need not be related to the positions of theelectrode combinations on the gastrointestinal organ, particularly wherestimulation is configured to produce distention, nausea or discomfort,and not to regulate motility by peristaltic function.

In the example of FIG. 7C, first and second stimulation 81, 83 areapplied via Channel 1 and Channel 2, respectively, with a time delaybetween cessation of delivery of the first stimulation delivery and thestart of delivery of the second stimulation, and vice versa. Hence, incontrast to the example of FIGS. 7A and 7B, the next stimulation doesnot commence immediately following the previous stimulation. Instead,there may be a delay between stimulation via different electrodecombinations. The delay may be greater than approximately one second,ten seconds, thirty seconds, one minute, or longer.

FIG. 7D shows the delivery of first and second stimulation 85, 87 viadifferent electrode combinations associated with Channels 1 and 2 withinthe same therapy window W on a time-interleaved basis. In this case,stimulation delivered during a therapy window, as described herein, isprovided by stimulation from two or more Channels, which aretime-interleaved with one another within the therapy window. In theexample of FIG. 7E, however, first and second stimulation 89, 91 aredelivered via different electrode combinations associated with Channels1 and 2 within different therapy windows W on a time-independent basis.For example, first stimulation may be delivered via a first electrodecombination for a first period of time associated with an entire therapywindow W, and then second stimulation may be delivered via a secondelectrode combination for a second period of time associated with anentire, different therapy window.

Again, the first and second stimulation therapies may comprise pulses,pulse trains, pulse bursts, burst patterns, or other patterns, and mayinclude various duty cycles. The first and second periods of time maygenerally refer to a period of time during which stimulation is activelydelivered via a given electrode combination, even though stimulation maybe delivered in different forms. Accordingly, delivery of stimulationfor a period of time does not necessarily require that stimulationpulses are delivered continuously during that time. Rather, it issufficient that stimulation be actively delivered, subject to gaps ordelays associated with pulses, bursts, burst patterns or other waveformsthat may be specified for the stimulation, e.g., as stimulationparameters.

FIGS. 8A, 8B and 8C are example timing diagrams illustrating bursts ofpulses having variations between the pulses of the bursts. As shown inFIG. 7A, burst pattern 76 includes multiple bursts 78A, 78B, 78C, 78Dand 78E (collectively “bursts 78) of discrete pulses. Burst pattern 76and bursts 78 may be similar to burst pattern 60 and bursts 62,respectively, as described in FIGS. 5A and 5B. Burst patterns as shownin FIGS. 8A-8C may be used in conjunction with otheranti-desensitization features, such as multi-site stimulation, therapywindows, and lockout intervals. The pulses of each of bursts 78 may varyin voltage amplitude within each burst such that at least two pulseswithin each burst have different voltage amplitudes. In addition, eachsubsequent burst may contain a sequence of pulses that is not identicalto the sequence of pulses of the previous burst. These variations involtage amplitude of the pulses may help to prevent or delaydesensitization. For example, the pulses of burst 78A are not identicalto the pulses delivered during burst 78B. While voltage amplitude is thestimulation parameter described in FIGS. 8A, 8B and 8C, the pulses mayvary by any stimulation parameter, such as current amplitude, pulsewidth, or pulse rate.

The pulses of bursts 78 vary within each burst randomly within apredetermined range. The resulting pulses may have any voltage amplitudewithin the range in order to vary the stimulation therapy. In otherexamples, the variation between pulses may be limited according to aweighted randomization to a target magnitude and/or limited to themagnitude of change between consecutive pulses. For example, theweighted randomization may generate pulses with a large percentage ofpulses having a voltage amplitude near the target magnitude.Alternatively, the difference in magnitude between subsequent pulses maybe limited to a predetermined value or a percentage of the precedingpulse.

In addition to varying of voltage amplitude between pulses within eachburst 78, bursts 78 of burst pattern 76 may contain pulses havingdifferent voltage amplitudes between subsequent bursts. In this manner,variation of voltage amplitude between pulses continues into subsequentbursts in order to produce bursts having continually changing pulses. Inalternative embodiments, burst pattern 76 may only have variations inpulse voltage amplitude between pulses of the same burst. In otherwords, burst 78A has at least two pulses with different voltageamplitude and burst 78A is then repeated throughout burst pattern 76.Further, some other examples of burst pattern 76 may include at leasttwo bursts having identical pulses.

FIG. 8B shows burst pattern 80 having multiple bursts 82A, 82B, 82C, 82Dand 82E (collectively “bursts 82”). Burst pattern 80 is similar to burstpattern 76. However, bursts 82 of burst pattern 80 each may have pulsesof the same voltage amplitude within each of the bursts. Aanti-desensitization measure implemented in burst pattern 80 is that thevoltage amplitude of the pulses only varies between subsequent bursts,not within any burst. As shown in FIG. 8B, the voltage amplitude of thepulses in burst 82A is smaller than the voltage amplitude of the pulsesin burst 82B. In this manner, the tissue affected by the stimulationpulses may not become desensitized to bursts having the same voltageamplitude throughout therapy. The variation in pulses provided withinburst pattern 80 may be governed by stimulator 12 in a similar manner asdescribed in FIG. 8A. In other examples of burst pattern 80, two or morebursts may have pulses of the same voltage amplitude.

FIG. 8C shows multiple burst patterns 84A and 84B delivered to patient16. Stimulator 12 may implement a desensitization measure that furthervaries the pulses of bursts throughout the treatment of the patient. Insome examples, burst pattern 76 and 80 described above may be repeatedwhenever gastric stimulation is delivered to patient 16. In contrast,burst patterns 84A and 84B of FIG. 8C deliver bursts having pulses withdifferent voltage amplitudes of the pulses. Burst pattern 84A containsat least burst 86A and 86B. The first burst 86A has pulses with smallervoltage amplitudes than pulses of burst 86B. Burst pattern 84B isdifferent than burst pattern 84A such that first burst 88A has pulseswith greater voltage amplitudes than the pulses of burst 88B. Whileburst patterns 84A and 84 may include two bursts or greater than onehundred bursts, stimulator 12 or programmer 14 may vary at least oneburst between the two burst patterns in order to implement thedesensitization measure.

While the bursts shown in FIGS. 8A, 8B and 8C, each have six pulses,bursts delivered to patient 16 may have any number of pulses as desiredby the clinician to treat the patient. In addition, burst patterns 76,80, 84A or 84B may have any number of bursts. The number of burstswithin subsequent burst patterns may vary with the length of each burstpattern and/or the duty cycle of the pulses and bursts. In any case,stimulator 12 may vary at least one stimulation parameter within aburst, burst pattern, or treatment of patient 16 in order to implement adesensitization measure. This implementation is not directed to changingthe efficacy of therapy. Rather, the variation of stimulation parametersis directed to extending the efficacy of therapy by preventing theconstant delivery of identical stimulation therapy to a tissue site orsites.

FIG. 9 is a flow diagram illustrating a method for delivering gastricstimulation therapy according to a lockout period that extends theefficacy of the therapy. It will be apparent that the method illustratedin FIG. 9 may be implemented within a patient programmer, a gastricelectrical stimulator, or a combination of both. In general, one of theprogrammer or the stimulator receives a request to deliver theelectrical gastric stimulation therapy to the patient, prohibitsdelivery of the gastric stimulation therapy by the stimulator if therequest is received within a lockout period following a previousdelivery of gastric stimulation therapy, and permits delivery of thegastric stimulation therapy by the stimulator if the request is notreceived within a lockout period following the previous delivery ofgastric stimulation therapy.

As shown in FIG. 9, system 10 stands ready in standby mode where thesystem is ready to deliver therapy when needed (90). If system 10 doesnot receive a request or indication for stimulation therapy (92), thesystem remains in standby mode. If system 10 receives a request todeliver stimulation (92), e.g., by user input into patient programmer14, a command received by stimulator 12 from patient programmer 14, or acommand generated automatically within stimulator 12 or programmer 14,e.g., for delivery of stimulation at a scheduled time, system 10 checksto determine if the stimulation request is made at a permitted time on atherapy schedule (94).

If not, then patient programmer 14 may deliver a prohibited time messageto patient 16 (96), advising the patient that stimulation is notpermitted. In this manner, patient programmer 14 or stimulator 12prohibit delivery of gastric stimulation therapy if a request is notreceived within a time period specified by the therapy schedule. Thesystem 10 then may return to standby mode (90). If the stimulationrequest is made at a permitted time (94), then patient programmer 14 maydetermine if stimulation is nevertheless locked out via a lockout period(98) following a termination of a previous application of therapy. Ifsystem 10 is locked out from delivering therapy, system 10 delivers alockout message to patient 16, e.g., via patient programmer 14, thatindicates therapy cannot be delivered at this time (100). System 10 thenmay return to standby mode (90).

If system 10 is not locked out, the system delivers electricalstimulation to patient 16 via stimulator 12 (102). If a stop request isreceived (104), e.g., from patient 16 via patient programmer 14, thepatient programmer instructs stimulator 12 to stop stimulation (106).Similarly, if a stop request has not been received but an applicabletherapy window has expired (104), patient programmer 14 instructsstimulator 12 to stop stimulation (106). In this manner, stimulator 12may receive an instruction from programmer 14 to generate thestimulation for the first period of time corresponding to the therapywindow. Alternatively, stimulator 12 may voluntarily stop stimulation ifthe stimulator is configured to track the therapy window. If no stoprequest is received, and the therapy window has not expired, stimulator12 continues to deliver therapy (102). Again, the therapy window may beselected to be a length of time sufficient to cause a desiredtherapeutic effect for a desired period of time, taking into account anyprolonged therapeutic effect that may during a recovery period followingcessation of the stimulation therapy.

When stimulation is complete and stimulator 12 stops deliveringelectrical stimulation to patient 16 (106), system 10 sets the lockoutperiod according to the lockout instructions stored by system 10 (108),e.g., in patient programmer 14 or stimulator 12. System 10 then anyreturn to standby mode until stimulation therapy is to be deliveredagain (90). In some embodiments, system 10 may also implement additionalanti-desensitization features to further extend the efficacy of gastricstimulation therapy. For example, in addition to the lockout, therapyschedule and therapy window features, programmer 14 and/or stimulator 12may deliver stimulation using burst pattern parameter selection, a burstpattern variation feature, or multi-site features.

FIG. 10 is a flow diagram illustrating a method for delivering gastricstimulation therapy according to a selection of electrode combinationsto extend the efficacy of the therapy. It will be apparent that themethod illustrated in FIG. 10 may be implemented within a patientprogrammer, a gastric electrical stimulator, or a combination of both.As shown in FIG. 10, system 10 remains in standby mode until a requestfor stimulation delivery is received (110). The request may be a patientinput that requests stimulation therapy, which may be entered intopatient programmer 14. Alternatively, the request may be a commandtransmitted by patient programmer 14 to stimulator 12. As a furtheralternative, the request may be a command generated automatically withinpatient programmer 14 or stimulator 12. In this example, system 10generates a selection of electrodes, either in patient programmer 14 orstimulator 12, by automatically selecting new, available electrodes forelectrical stimulation (112) according to a predetermined order, arandom selection function, or a pseudo-random selection function. Theelectrodes may be selected from one or more arrays of multipleelectrodes, e.g., as shown in FIG. 4, to form different electrodecombinations for use in multi-site stimulation.

Random or pseudo-random selection may be used within programmer 14and/or stimulator 12 to produce a selected combination of electrodes fordelivery of stimulation. Alternatively, instead of random orpseudo-random selection, system 10 may select the electrodes accordingto a predetermined progression or scheme, which may be defined by aclinician. In either case, the selection is automatic by programmer 14or stimulator 12. The electrode selection may be made by patientprogrammer 14, in which case the patient programmer transmits theselection to stimulator 12 for use in delivery of stimulation.Alternatively, stimulator 12 may voluntarily select the electrodes whenpatient programmer 14 instructs the stimulator to start stimulation. Ineach case, the electrode selection may be subject to constraints suchthat electrodes selected at different tissue sites are still sufficientto achieve a desired therapeutic effect.

The new electrodes associated with a newly selected electrodecombination should be different from the electrodes in the electrodecombination used for the last stimulation application, and should targeta different stimulation site. The last stimulation may refer tostimulation delivered in a previous scheduled period S on the therapyschedule, during a previous therapy window W, during a previous timesegment within a therapy window, or otherwise. For example, theelectrode combination selection may be changed from one therapy windowto another such that successive applications of stimulation therapy usedifferent electrode combinations. Alternatively, the electrode selectionmay be changed from one scheduled time period to another, e.g., suchthat a patient receives stimulation via different electrodes atbreakfast, lunch, dinner or other time periods.

The process of FIG. 10 also may be applicable to techniques that do nomake use of therapy schedules, therapy windows, or the like. As analternative, different sets of electrodes may be selected as electrodecombinations for successive applications of stimulation, without regardto the manner in which the timing of the stimulation is determined. Ineach case, use of the same electrodes as electrode combinations isavoided for consecutive stimulation applications. In addition, theelectrode selection may be changed for one pulse burst to another or forone burst pattern to another within the same therapy window or scheduledtime period. As a further alternative, electrode selection may bechanged at periodic intervals during the course of delivery ofstimulation, e.g., every n seconds or minutes. Each electrodecombination may be used to deliver stimulation for a period of time ofgreater than or equal to thirty seconds.

Stimulator 12 delivers electrical stimulation to patient 16 via the newselection of electrodes (114), either automatically or as instructed bypatient programmer 14. Once electrical stimulation is complete (116),e.g., as a result of a patient request to stop stimulation or expirationof a therapy window, scheduled time period (FIG. 9), or other applicabletime limit (such as a specified period of time for use of the electrodecombination), stimulator 12 stops stimulation to cease therapy (118).Patient programmer 14 then may store stimulation delivery informationfor use or review at a later time (120). Stimulation deliveryinformation may include any data relevant to the therapy. For example,stimulation delivery information may include stimulation parameters suchas voltage, current, pulse width, pulse frequency, burst rate, andselection of electrodes. In addition, stimulation delivery informationmay also include any patient input to patient programmer 14, such asadditional requests for stimulation or changes in stimulation amplitudeduring therapy.

While random selection of electrode combinations may be useful, patientprogrammer 14 may select electrode combinations based upon any of avariety of methods desired by the clinician. For example, patientprogrammer 14 may select electrodes by cycling through availableelectrodes, selecting electrodes according to an algorithm designed tolimit desensitization of tissue, or some other method. As one example, aclinician or other caregiver may directly specify a fixed progressionamong successive, selected electrode combinations. In any case, patientprogrammer 14 or stimulator 12 changes the selection of electrodecombinations to support multi-site stimulation as anotheranti-desensitization feature directed to extending the efficacy of thegastric stimulation therapy. The selection of different electrodecombinations as an anti-desensitization feature, e.g., as illustrated inFIG. 10, may be practiced independently or in conjunction with otheranti-desensitization features, e.g., lockout, therapy window, therapyschedule, and burst pattern parameter selection.

FIG. 11 is a flow diagram illustrating a method for delivering gastricstimulation therapy at with varying start times, end times, ordurations. The method of FIG. 11 may be implemented within programmer 14and/or stimulator 12 to adjust, e.g., timing and duration of burstpatterns, or timing and duration of permitted time periods on a therapyschedule. As mentioned previously, start times and/or end timesassociated with permitted time periods on a therapy schedule may beadjusted. In this manner, the therapy schedule may ensure thatstimulation is delivered not only at selected times, rather thancontinuously, but also at selected, variable times. Also, as mentionedprevious, the number, timing and duration of burst patterns may beadjusted whether burst patterns are used in conjunction with a therapyschedule and therapy windows, or not.

In the example of FIG. 11, stimulator 12 or programmer 14 may select aweighted randomized start time for the next stimulation delivery (122),which may be coincident with the next permitted period of time on atherapy schedule, if applicable. Processors within stimulator 12 orprogrammer 14 may access instructions within memory to perform the starttime selection process. The instructions may be in the form of a set ofequations, for example, that weight the start times to a target starttime so that the randomization of start times does not drift away from apreferred start time for therapy. For example, the instructions may beconfigured to generate a high percentage of start times within apredetermined number of minutes (e.g., 10 to 15 minutes) of the targetstart time. The clinician may alter the instructions at initialprogramming or throughout therapy.

The selected start time may vary relative to the start time for aprevious stimulation delivery that was delivered, e.g., in a previousperiod P. In particular, the start time of a previous stimulationdelivery in the same period P may not be relevant. Rather, the starttime may be selected so that stimulation is not delivered at the sametime during every period P, e.g., at the same time every day. Forexample, the start time of stimulation delivered around lunch time for agiven day is varied relative to the start time of stimulation deliveryaround lunch time the previous day.

In addition to selecting a start time, stimulator 12 and/or programmer14 may determine an end time using a similar technique, so that aduration of the stimulation delivery can be varied. Alternatively, theduration may be fixed while the start time is varied to change thetiming of the stimulation delivery. Selecting different start time andend time may be useful for varying the timing and duration of burstpatterns that are delivered with or without regard to a therapy scheduleor therapy windows.

Variation of start time and/or end time ensures that the nextstimulation delivery will not occur at the same time as thecorresponding stimulation delivery in the previous period P. Forexample, if the corresponding start time was 9:05 AM the previous day,stimulator 12 or programmer 14 may be programmed select a start time soas to avoid a second day of starting therapy at 9:05 AM. Stimulator 12or programmer 14 may store the selected start and/or end time value(s)in memory to determine the start of the next permitted period of time inthe therapy schedule for delivery of therapy (124).

Stimulator 12 or programmer 14 then uses the selected values to definethe next stimulation to be delivered (126). Therapy is then deliveredwhen an internal clock or other timing device indicates that the timematches the selected start time in memory (128). If the stimulationdelivery is not complete (130), e.g., no stop request, therapy windowexpiration, or therapy schedule time expiration applies, stimulator 12continues stimulation delivery (128). Once stimulation is complete(130), stimulator 12 stops stimulation delivery to patient 16 (132) andselects the next start and/or end time value (122).

While stimulator 12 or programmer 14 are described in FIG. 11 as using aweighted randomized start time, stimulator 12 may vary the start timewith any method desired by the clinician. For example, the start timesmay be cycled between multiple reselected start times, randomly selectedwithin a given start time range, or selected based upon several previousstart times to ensure start time variation. In any case, the variationof start times may prevent the stimulated tissue from becomingaccustomed to stimulation at a certain static time during the day. Inaddition, variation of start times may prevent patient 16 from alteringtheir eating habits to accommodate the stimulation therapy deliverytimes.

FIG. 12 is a flow diagram illustrating a method for selecting differentburst pattern characteristics to extend efficacy of therapy. As shown inFIG. 12, programmer 14 and/or stimulator 12 may select a variable burstpattern number (134), variable burst pattern durations (136) andvariable burst pattern start times (138) for each therapy period orwindow. In this manner, different numbers of burst patterns can bedelivered in different therapy periods, e.g., different days. Inaddition, the burst patterns on different days may have differentdurations and start times. Likewise, if stimulator 12 is configured todelivered more than one burst pattern within a therapy window, thenumber, duration and start times of the burst patterns may be varied. Inthis manner, burst patterns can be modified to assist in preventing ordelaying desensitization.

FIG. 13 is a flow diagram illustrating application of a therapy windowfeature as described herein for gastric electrical stimulation to extendefficacy of therapy. In the example of FIG. 13, a period of time for adesired therapeutic effect is selected (142). For example, a physicianor patient may select the time of the desired therapeutic effect topersist, e.g., via a programmer. A programmer or stimulator determines atherapy window that is sufficient to produce the desired therapeuticeffect for the selected period of time (144), e.g., given a set ofstimulation parameters. For example, the programmer or stimulator mayrefer to preestablished data mapping the selected period of time to oneof a plurality of therapy windows, or apply a mathematical function thatcomputes a therapy window for the selected period of time. The data orfunction may be formulated based on theoretical or empirical dataobtained for the patient or for a class of patients. Again, differenttherapy windows, i.e., of different lengths, may be predetermined fordifferent therapeutic effects and different periods of time for whichthe therapeutic effects are desired. Accordingly, when a desiredtherapeutic effect is desired for a particular period of time, theeffect and the time can be mapped to an appropriate therapy window usingthe preestablished mapping. The stimulator then delivers the stimulationfor the duration of the therapy window (146) to produce the desiredtherapeutic effect for the selected period of time, which extends beyondthe end of the therapy window.

FIG. 14 is a flow diagram illustrating application of a multi-sitestimulation feature as described herein for gastric electricalstimulation to extend efficacy of therapy. In the example of FIG. 14, aprogrammer or stimulator configures first and second stimulationtherapies to produce a substantially identical therapeutic result (148),such as distention. For example, parameters associated with the firstand second stimulation may be programmed to produce the substantiallyidentical therapeutic result. In some cases, the parameters used for thefirst and second stimulation may be substantially identical. Thestimulator then may apply the first and second stimulation to differentsites via different electrode combinations. As shown in FIG. 14, thestimulator may deliver the first stimulation via a first electrodecombination for a first period of time greater than or equal toapproximately thirty seconds (150), and delivered the second stimulationvia a second electrode combination for a second period of time greaterthan or equal to approximately thirty seconds (152). The first andsecond periods of time may partially overlap or not overlap, and may bethe same or different in duration.

The techniques described in this disclosure may be implemented inhardware, software, firmware or any combination thereof. For example,various aspects of the techniques may be implemented within one or moremicroprocessors, digital signal processors (DSPs), application specificintegrated circuits (ASICs), field programmable logic arrays (FPGAs), orany other equivalent integrated or discrete logic circuitry, as well asany combinations of such components. The term “processor” or “processingcircuitry” may generally refer to any of the foregoing logic circuitry,alone or in combination with other logic circuitry, or any otherequivalent circuitry.

When implemented in software, the functionality ascribed to the systemsand devices described in this disclosure may be embodied as instructionson a computer-readable medium such as random access memory (RAM),read-only memory (ROM), non-volatile random access memory (NVRAM),electrically erasable programmable read-only memory (EEPROM), FLASHmemory, magnetic media, optical media, or the like. The instructions areexecuted to support one or more aspects of the functionality describedin this disclosure.

Various aspects of the disclosure have been described. These and otheraspects are within the scope of the following claims.

1. A method for gastric stimulation with reduced desensitization, themethod comprising: delivering first electrical stimulation therapy to agastrointestinal organ of a patient via a first electrode combinationpositioned at a first position on the gastrointestinal organ for a firstperiod of time greater than or equal to approximately 30 seconds; anddelivering second electrical stimulation therapy to the gastrointestinalorgan via a second electrode combination positioned at a second positionon the gastrointestinal organ for a second period of time greater thanor equal to approximately 30 seconds, wherein the first and secondelectrical stimulation therapies are configured to produce asubstantially identical therapeutic result.
 2. The method of claim 1,wherein each of the first and second periods of times is greater than orequal to approximately one minute.
 3. The method of claim 1, whereineach of the first and second periods of times is greater than or equalto approximately five minutes.
 4. The method of claim 1, wherein thefirst and second periods of time do not overlap.
 5. The method of claim1, wherein the first and second periods of time partially overlap. 6.The method of claim 1, further comprising delivering the first andsecond electrical stimulation therapy on one of a time-alternating basisto provide a combined stimulation therapy delivery that produces thetherapeutic result, or a time-independent basis to provide separatestimulation therapy deliveries that produce the therapeutic result. 7.The method of claim 1, wherein the first and second electrodecombinations are displaced at least approximately 3 cm from one another.8. The method of claim 1, wherein the gastrointestinal organ includesone of a stomach or a small intestine of the patient, and thestimulation parameters associated with the first and second electricalstimulation therapy are substantially identical.
 9. The method of claim1, further comprising: delivering third electrical stimulation therapyto the gastrointestinal organ via a third electrode combinationpositioned at a third position on the gastrointestinal organ at a thirdtime, repeating the delivery of the first, second and third electricalstimulation therapies for the first, second and third periods of time;and selecting an order of the first, second and third periods of time ina varying order for at least some of the repeated deliveries, whereinthe first, second and third electrical stimulation therapies areconfigured to produce a substantially identical therapeutic result, andwherein the first, second and third positions are arranged such that thefirst position is most proximal on the gastrointestinal organ, the thirdposition is most distal on the gastrointestinal organ, and the secondposition is between the first and third positions.
 10. The method ofclaim 1, wherein the substantially identical therapeutic effect includespromotion of gastric distention or discomfort to discourage food intakeby the patient.
 11. A gastrointestinal electrical stimulation devicecomprising: a first electrode combination implantable at a firstposition on a gastrointestinal organ of a patient; a second electrodecombination implantable at a second position on the gastrointestinalorgan; and a stimulation generator that delivers first electricalstimulation therapy to the gastrointestinal organ via the firstelectrode combination for a first period of time greater than or equalto approximately 30 seconds, and delivers second electrical stimulationtherapy to the gastrointestinal organ via a second electrode combinationfor a second period of time greater than or equal to approximately 30seconds, wherein the first and second electrical stimulation therapiesare configured to produce a substantially identical therapeutic result.12. The device of claim 11, wherein each of the first and second periodsof times is greater than or equal to approximately one minute.
 13. Thedevice of claim 11, wherein each of the first and second periods oftimes is greater than or equal to approximately five minutes.
 14. Thedevice of claim 11, wherein the first and second periods of time do notoverlap.
 15. The device of claim 11, wherein the first and secondperiods of time partially overlap.
 16. The device of claim 11, whereinthe stimulation generator delivers the first and second electricalstimulation therapy on one of a time-alternating basis to provide acombined stimulation therapy delivery that produces the therapeuticresult, or a time-independent basis to provide separate stimulationtherapy deliveries that produce the therapeutic result.
 17. The deviceof claim 11, wherein the gastrointestinal organ includes one of astomach or a small intestine of the patient, and the stimulationparameters associated with the first and second electrical stimulationtherapy are substantially identical.
 18. The device of claim 11, whereinthe stimulation generator delivers third electrical stimulation therapyto the gastrointestinal organ via a third electrode combinationpositioned at a third position on the gastrointestinal organ at a thirdtime, repeats the delivery of the first, second and third electricalstimulation therapies for the first, second and third periods of time,and selects an order of the first, second and third periods of time in avarying order for at least some of the repeated deliveries, wherein thefirst, second and third electrical stimulation therapies are configuredto produce a substantially identical therapeutic result.
 19. The deviceof claim 11, wherein the substantially identical therapeutic effectincludes promotion of gastric distention or discomfort to discouragefood intake by the patient.
 20. A gastrointestinal electricalstimulation device comprising: means for delivering first electricalstimulation therapy to a gastrointestinal organ of a patient via a firstelectrode combination positioned at a first position on thegastrointestinal organ for a first period of time greater than or equalto approximately 30 seconds; and means for delivering second electricalstimulation therapy to the gastrointestinal organ via a second electrodecombination positioned at a second position on the gastrointestinalorgan for a second period of time greater than or equal to approximately30 seconds, wherein the first and second electrical stimulationtherapies are configured to produce a substantially identicaltherapeutic result.
 21. The device of claim 20, wherein each of thefirst and second periods of times is greater than or equal toapproximately one minute.
 22. The device of claim 20, wherein each ofthe first and second periods of times is greater than or equal toapproximately five minutes.
 23. The device of claim 20, wherein thefirst and second periods of time do not overlap.
 24. The device of claim20, wherein the first and second periods of time partially overlap. 25.The device of claim 20, further comprising means for delivering thefirst and second electrical stimulation therapy on one of atime-alternating basis to provide a combined stimulation therapydelivery that produces the therapeutic result, or a time-independentbasis to provide separate stimulation therapy deliveries that producethe therapeutic result.
 26. The device of claim 20, wherein thegastrointestinal organ includes one of a stomach or a small intestine ofthe patient, and the stimulation parameters associated with the firstand second electrical stimulation therapy are substantially identical.27. The device of claim 20, further comprising: means for deliveringthird electrical stimulation therapy to the gastrointestinal organ via athird electrode combination positioned at a third position on thegastrointestinal organ at a third time, means for repeating the deliveryof the first, second and third electrical stimulation therapies for thefirst, second and third periods of time; and means for selecting anorder of the first, second and third periods of time in a varying orderfor at least some of the repeated deliveries, wherein the first, secondand third electrical stimulation therapies are configured to produce asubstantially identical therapeutic result.
 28. The device of claim 20,wherein the substantially identical therapeutic effect includespromotion of gastric distention or discomfort to discourage food intakeby the patient.